lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

Proto-oncogene c-Myb potentiates cisplatin resistance of ovarian cancer cells by downregulating lncRNA NKILA and modulating cancer stemness and LIN28A-let7 axis.

Ovarian cancer is a major gynecological cancer that has poor prognosis associated mainly to its late diagnosis. Cisplatin is an FDA approved ovarian cancer therapy and even though the therapy is initially promising, the patients mostly progress to resistance against cisplatin. The underlying mechanisms are complex and not very clearly understood. Using two different paired cell lines representing cisplatin-sensitive and the cisplatin-resistant ovarian cancer cells, the ES2 and the A2780 parental and cisplatin-resistant cells, we show an elevated proto-oncogene c-Myb in resistant cells. We further show down-regulated lncRNA NKILA in resistant cells with its de-repression in resistant cells when c-Myb is silenced. NKILA negatively correlates with cancer cell and invasion but has no effect on cellular proliferation or cell cycle. C-Myb activates NF-κB signaling which is inhibited by NKILA. The cisplatin resistant cells are also marked by upregulated stem cell markers, particularly LIN28A and OCT4, and downregulated LIN28A-targeted let-7 family miRNAs. Whereas LIN28A and downregulated let-7s individually de-repress c-Myb-mediated cisplatin resistance, the ectopic expression of let-7s attenuates LIN28A effects, thus underlying a c-Myb-NKILA-LIN28A-let-7 axis in cisplatin resistance of ovarian cancer cells that needs to be further explored for therapeutic intervention.

Foetal haemoglobin elevation, unfavourable prognosis, and protective role of genetic variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 in children with ALL.

In acute lymphoblastic leukaemia (ALL), elevated foetal haemoglobin (HbF) levels have been associated with the prognosis of patients. Genetic variants in HbF regulatory genes: BAF chromatin remodelling complex subunit (BCL11A), HBS1L-MYB transcriptional GTPase intergenic region (HBS1L-MYB), Krüppel-like factor 1 (KLF1), haemoglobin gamma subunit 2 (HBG2), haemoglobin gamma subunit 1 (HBG1), and haemoglobin subunit beta pseudogene 1 (HBBP1) are often associatedwith elevatedHbF concentration. This study investigated the association of genetic variants in HbF regulatory genes with HbF concentration, unfavourable prognosis, and outcome in children with ALL.We quantified HbF concentration and genotyped 17 genetic variants in 48 patients with ALL and 64 children without ALL as a reference group. HbF concentrationwas higher in patients than in the reference group (4.4%vs 1.4%), and 75%(n = 36) of thepatientshadHbF>2.5%.Unfavourable prognosis ALL was established in 68.8% (n = 33) of the patients. Variant HBG2 rs7482144 was associated with high HbF concentration (P = 0.015); while HBS1L-MYB rs9399137 (P = 0.001), HBG2 rs7482144 (P = 0.001) and the ß-globin genes HBG2, HBG1, and HBPP1 haplotypeTGC(P = 0.017) with unfavourable prognosisALL.Additionally, variantBCL11A rs4671393 showed a protective role (P = 0.0001). In conclusion, variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 may play a significant role in ALL.

The interaction of Pu.1 and cMyb in zebrafish neutrophil development.

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited. PU.1 and cMYB participate in multiple stages of neutrophil development, and their abnormalities are often associated with hematologic disorders. However, the regulatory relationship between these factors in vivo and their mode of interaction remain unclear. In this study, zebrafish models with cMyb overexpression (cmybhyper) and Pu.1 deficiency (pu.1G242D/G242D) were utilized to systematically investigate the interaction between Pu.1 and cMyb during granulopoiesis through whole-mount in situ hybridization, qRT-PCR, fluorescence reporting systems, and rescue experiments. The results showed a significant increase in cmyb expression in neutrophils of the pu.1G242D/G242D mutant, while there was no apparent change in pu.1 expression in cmybhyper. Further experiments involving injection of morpholino (MO) to decrease cmyb expression in pu.1G242D/G242D mutants, followed by SB and BrdU staining to assess neutrophil quantity and proliferation, revealed that reducing cmyb expression could rescue the abnormal proliferation phenotype of neutrophils in the pu.1G242D/G242D mutant. These findings suggest that Pu.1 negatively regulates the expression of cMyb during neutrophil development. Finally, through the construction of multi-site mutation plasmids and a fluorescent reporter system, confirmed that Pu.1 directly binds to the +72 bp site in the cmyb promoter, exerting negative regulation on its expression. In conclusion, this study delineates that Pu.1 participates in neutrophil development by regulating cmyb expression. This provides new insights into the regulatory relationship between these two factors and their roles in diseases.

Transcription Factor MYB as Therapeutic Target: Current Developments.

The MYB protein is a pivotal player in the cellular transcriptional network, influencing major important processes such as cell proliferation, differentiation, and apoptosis. Because of its role in oncogenesis, MYB is now a compelling target for therapeutic interventions in cancer research. This review summarizes its molecular functions and current therapeutic approaches aiming to inhibit its oncogenic activity.

Acquired immune resistance is associated with interferon signature and modulation of KLF6/c-MYB transcription factors in myeloid leukemia.

Resistance to immunity is associated with the selection of cancer cells with superior capacities to survive inflammatory reactions. Here, we tailored an ex vivo immune selection model for acute myeloid leukemia (AML) and isolated the residual subpopulations as "immune-experienced" AML (ieAML) cells. We confirmed that upon surviving the immune reactions, the malignant blasts frequently decelerated proliferation, displayed features of myeloid differentiation and activation, and lost immunogenicity. Transcriptomic analyses revealed a limited number of commonly altered pathways and differentially expressed genes in all ieAML cells derived from distinct parental cell lines. Molecular signatures predominantly associated with interferon and inflammatory cytokine signaling were enriched in the AML cells resisting the T-cell-mediated immune reactions. Moreover, the expression and nuclear localization of the transcription factors c-MYB and KLF6 were noted as the putative markers for immune resistance and identified in subpopulations of AML blasts in the patients' bone marrow aspirates. The immune modulatory capacities of ieAML cells lasted for a restricted period when the immune selection pressure was omitted. In conclusion, myeloid leukemia cells harbor subpopulations that can adapt to the harsh conditions established by immune reactions, and a previous "immune experience" is marked with IFN signature and may pave the way for susceptibility to immune intervention therapies.

DREAM a little dREAM of DRM: Model organisms and conservation of DREAM-like complexes: Model organisms uncover the mechanisms of DREAM-mediated transcription regulation.

DREAM complexes are transcriptional regulators that control the expression of hundreds to thousands of target genes involved in the cell cycle, quiescence, differentiation, and apoptosis. These complexes contain many subunits that can vary according to the considered target genes. Depending on their composition and the nature of the partners they recruit, DREAM complexes control gene expression through diverse mechanisms, including chromatin remodeling, transcription cofactor and factor recruitment at various genomic binding sites. This complexity is particularly high in mammals. Since the discovery of the first dREAM complex (drosophila Rb, E2F, and Myb) in Drosophila melanogaster, model organisms such as Caenorhabditis elegans, and plants allowed a deeper understanding of the processes regulated by DREAM-like complexes. Here, we review the conservation of these complexes. We discuss the contribution of model organisms to the study of DREAM-mediated transcriptional regulatory mechanisms and their relevance in characterizing novel activities of DREAM complexes.

Genomic survey of MYB gene family in six pearl millet (Pennisetum glaucum) varieties and their response to abiotic stresses.

In addition to their roles in developmental and metabolic processes, MYB transcription factors play crucial roles in plant defense mechanisms and stress responses. A comprehensive analysis of six pearl millet genomes revealed the presence of 1133 MYB genes, which can be classified into four phylogenetically distinct subgroups. The duplication pattern of MYB genes across the pearl millet genomes demonstrates their conserved and similar evolutionary history. Overall, MYB genes were observed to be involved in drought and heat stress responses, with stronger differential expressed observed in root tissues. Multiple analyses indicated that MYB genes mediate abiotic stress responses by modulating abscisic acid-related pathways, circadian rhythms, and histone modification processes. A substantial number of duplicated genes were determined to exhibit differential expression under abiotic stress. The consistent positive expression trend observed in duplicated gene pairs, such as PMA5G04432.1 and PMA2G00728.1, across various abiotic stresses suggests that duplicated MYB genes plays a key role in the evolution of adaptive responses of pearl millet to abiotic stresses.

The prognostic and immunological role of MYB: from bladder cancer validation to pan-cancer analysis.

BACKGROUND: MYB proto-oncogene is verified as a transcription factor. Although emerging evidence showed that MYB plays a critical part in tumor progression and immunity, a systematic pan-cancer analysis of MYB still remains to be performed for determining whether MYB could serve as a biomarker for cancer screening, prognosis prediction and accurate therapy design in various human cancers. METHODS: In the present study, we performed qRT-PCR, wound healing assay and transwell assay to validate the expression level and biological function of MYB in bladder cancer. Then, we utilized several open-source databases including UCSC Xena database, TCGA, GTEx, etc. Online tools was used to process the raw data from UCSC Xena database. RESULTS: We found that the expression level of MYB is significantly higher in bladder cancer cell lines than urothelial cells. Further experiments confirmed that overexpression of MYB enhanced the ability of migration in bladder cancer. Next, we found that the expression level of MYB is significantly higher in most cancers. Meanwhile, MYB expression was positively or negatively related with the prognosis in different cancer types. In addition, MYB expression is significantly related to immune score and immune cells in most cancer types. Moreover, MYB act as an immunotherapy biomarker superior to several traditional immunotherapy biomarkers. Finally, deep deletion was the most frequent genetic alteration of MYB. CONCLUSION: MYB may serve as a powerful biomarker for tumor screening, prognostic, individualized treatment strategy in a broad range of malignancies.

The frequency and differential pleiotropy of phenotypic nonspecificity in Drosophila melanogaster.

The regulation of the initiation of transcription by transcription factors is often assumed to be dependent on specific recognition of DNA-binding sites and nonredundant. However, the redundant induction or rescue of a phenotype by transcription factors, phenotypic nonspecificity, challenges these assumptions. To assess the frequency of phenotypic nonspecificity in the rescue of transcription factor phenotypes, seven transcription factor phenotypes (labial, Deformed, Sex combs reduced, Ultrabithorax, fruitless, doublesex, and apterous) were screened for rescue by the expression of 12, or more, nonresident transcription factors. From 308 assessments of rescue by nonresident transcription factors, 18 rescues were identified across 6 of the 7 transcription factor phenotypes. Seventeen of the 18 rescues were with transcription factors that recognize distinct DNA-binding sites relative to the resident transcription factors. All rescues were nonuniform across pleiotropic transcription factor phenotypes suggesting extensive differential pleiotropy of the rescue. Primarily using RNAi to knockdown expression, and with the exceptions of the requirement of Bric a Brac 1 for female abdominal pigmentation and Myb oncogene-like for wing development, no evidence was found for a role of the other 16 nonresident transcription factor in the transcription factor phenotypes assessed. Therefore, these 16 rescues are likely due to functional complementation and not due to the expression of an epistatic function in the developmental/behavioral pathway. Phenotypic nonspecificity is both differentially pleiotropic and frequent, as on average 1 in 10-20 nonresident transcription factors rescue a phenotype. These observations will be important in future considerations of transcription factors function.

Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer.

Survival rates of patients with metastatic castration-resistant prostate cancer (mCRPC) are low due to lack of response or acquired resistance to available therapies, such as abiraterone (Abi). A better understanding of the underlying molecular mechanisms is needed to identify effective targets to overcome resistance. Given the complexity of the transcriptional dynamics in cells, differential gene expression analysis of bulk transcriptomics data cannot provide sufficient detailed insights into resistance mechanisms. Incorporating network structures could overcome this limitation to provide a global and functional perspective of Abi resistance in mCRPC. Here, we developed TraRe, a computational method using sparse Bayesian models to examine phenotypically driven transcriptional mechanistic differences at three distinct levels: transcriptional networks, specific regulons, and individual transcription factors (TF). TraRe was applied to transcriptomic data from 46 patients with mCRPC with Abi-response clinical data and uncovered abrogated immune response transcriptional modules that showed strong differential regulation in Abi-responsive compared with Abi-resistant patients. These modules were replicated in an independent mCRPC study. Furthermore, key rewiring predictions and their associated TFs were experimentally validated in two prostate cancer cell lines with different Abi-resistance features. Among them, ELK3, MXD1, and MYB played a differential role in cell survival in Abi-sensitive and Abi-resistant cells. Moreover, ELK3 regulated cell migration capacity, which could have a direct impact on mCRPC. Collectively, these findings shed light on the underlying transcriptional mechanisms driving Abi response, demonstrating that TraRe is a promising tool for generating novel hypotheses based on identified transcriptional network disruptions. SIGNIFICANCE: The computational method TraRe built on Bayesian machine learning models for investigating transcriptional network structures shows that disruption of ELK3, MXD1, and MYB signaling cascades impacts abiraterone resistance in prostate cancer.

MYB insufficiency disrupts proteostasis in hematopoietic stem cells, leading to age-related neoplasia.

MYB plays a key role in gene regulation throughout the hematopoietic hierarchy and is critical for the maintenance of normal hematopoietic stem cells (HSC). Acquired genetic dysregulation of MYB is involved in the etiology of a number of leukemias, although inherited noncoding variants of the MYB gene are a susceptibility factor for many hematological conditions, including myeloproliferative neoplasms (MPN). The mechanisms that connect variations in MYB levels to disease predisposition, especially concerning age dependency in disease initiation, are completely unknown. Here, we describe a model of Myb insufficiency in mice that leads to MPN, myelodysplasia, and leukemia in later life, mirroring the age profile of equivalent human diseases. We show that this age dependency is intrinsic to HSC, involving a combination of an initial defective cellular state resulting from small effects on the expression of multiple genes and a progressive accumulation of further subtle changes. Similar to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteasomal activity and elevated proliferation indicators, followed by elevated ribosome activity in young Myb-insufficient mice. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation.

Biphasic transcriptional and posttranscriptional regulation of MYB by androgen signaling mediates its growth control in prostate cancer.

MYB, a proto-oncogene, is overexpressed in prostate cancer (PCa) and promotes its growth, aggressiveness, and resistance to androgen-deprivation therapy. Here, we examined the effect of androgen signaling on MYB expression and delineated the underlying molecular mechanisms. Paralleling a dichotomous effect on growth, low-dose androgen induced MYB expression at both transcript and protein levels, whereas it was suppressed in high-dose androgen-treated PCa cells. Interestingly, treatment with both low- and high-dose androgen transcriptionally upregulated MYB by increasing the binding of androgen receptor to the MYB promoter. In a time-course assay, androgen induced MYB expression at early time points followed by a sharp decline in high-dose androgen-treated cells due to decreased stability of MYB mRNA. Additionally, profiling of MYB-targeted miRNAs demonstrated significant induction of miR-150 in high-dose androgen-treated PCa cells. We observed a differential binding of androgen receptor on miR-150 promoter with significantly greater occupancy recorded in high-dose androgen-treated cells than those treated with low-dose androgen. Functional inhibition of miR-150 relieved MYB suppression by high-dose androgen, while miR-150 mimic abolished MYB induction by low-dose androgen. Furthermore, MYB-silencing or miR-150 mimic transfection suppressed PCa cell growth induced by low-dose androgen, whereas miR-150 inhibition rescued PCa cells from growth repression by high-dose androgen. Similarly, we observed that MYB silencing suppressed the expression of androgen-responsive, cell cycle-related genes in low-dose androgen-treated cells, while miR-150 inhibition increased their expression in cells treated with high-dose androgen. Overall, these findings reveal novel androgen-mediated mechanisms of MYB regulation that support its biphasic growth control in PCa cells.

Recurrent noncoding somatic and germline WT1 variants converge to disrupt MYB binding in acute promyelocytic leukemia.

Genetic alternations can occur at noncoding regions, but how they contribute to cancer pathogenesis is poorly understood. Here, we established a mutational landscape of cis-regulatory regions (CREs) in acute promyelocytic leukemia (APL) based on whole-genome sequencing analysis of paired tumor and germline samples from 24 patients and epigenetic profiling of 16 patients. Mutations occurring in CREs occur preferentially in active enhancers bound by the complex of master transcription factors in APL. Among significantly enriched mutated CREs, we found a recurrently mutated region located within the third intron of WT1, an essential regulator of normal and malignant hematopoiesis. Focusing on noncoding mutations within this WT1 intron, an analysis on 169 APL patients revealed that somatic mutations were clustered into a focal hotspot region, including one site identified as a germline polymorphism contributing to APL risk. Significantly decreased WT1 expression was observed in APL patients bearing somatic and/or germline noncoding WT1 variants. Furthermore, biallelic WT1 inactivation was recurrently found in APL patients with noncoding WT1 variants, which resulted in the complete loss of WT1. The high incidence of biallelic inactivation suggested the tumor suppressor activity of WT1 in APL. Mechanistically, noncoding WT1 variants disrupted MYB binding on chromatin and suppressed the enhancer activity and WT1 expression through destroying the chromatin looping formation. Our study highlights the important role of noncoding variants in the leukemogenesis of APL.

c-Myb-mediated inhibition of miR-601 in facilitating malignance of osteosarcoma via augmentation of PKMYT1.

The crosstalk between osteosarcoma (OS) development and abnormally expressed microRNA (miR)-601 is not explored explicitly. Here, we identified the downregulated miR-601 in osteosarcoma (OS) through a comprehensive bioinformatics analysis of GEO Datasets. The results indicated that miR-601 was downregulated in both OS cells and tissues. The OS patients with reduced expression of miR-601 displayed worse prognosis. The results of in vitro and in vivo assay revealed that elevated miR-601 inhibited the proliferative, migratory and invasive capacities in OS cells. Mechanically, miR-601 exerted its function via targeting oncogene protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) at post-transcriptional level. Moreover, miR-601 was attenuated by c-Myb at transcriptional level. Taken together, our studies reveal that miR-601 is a suppressive gene negatively correlated with malignancy of OS.

Identification of a c-MYB-directed therapeutic for acute myeloid leukemia.

A significant proportion of patients suffering from acute myeloid leukemia (AML) cannot be cured by conventional chemotherapy, relapsed disease being a common problem. Molecular targeting of essential oncogenic mediators is an attractive approach to improving outcomes for this disease. The hematopoietic transcription factor c-MYB has been revealed as a central component of complexes maintaining aberrant gene expression programs in AML. We have previously screened the Connectivity Map database to identify mebendazole as an anti-AML therapeutic targeting c-MYB. In the present study we demonstrate that another hit from this screen, the steroidal lactone withaferin A (WFA), induces rapid ablation of c-MYB protein and consequent inhibition of c-MYB target gene expression, loss of leukemia cell viability, reduced colony formation and impaired disease progression. Although WFA has been reported to have pleiotropic anti-cancer effects, we demonstrate that its anti-AML activity depends on c-MYB modulation and can be partially reversed by a stabilized c-MYB mutant. c-MYB ablation results from disrupted HSP/HSC70 chaperone protein homeostasis in leukemia cells following induction of proteotoxicity and the unfolded protein response by WFA. The widespread use of WFA in traditional medicines throughout the world indicates that it represents a promising candidate for repurposing into AML therapy.

LncRNA BC200/miR-150-5p/MYB positive feedback loop promotes the malignant proliferation of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a group of heterogeneous hematologic malignancies with a risk of transformation to acute myeloid leukemia. Understanding the molecular mechanisms of the specific roles of long noncoding RNAs (lncRNAs) in MDS would create novel ways to identify diagnostic and therapeutic targets. The lncRNA BC200 is upregulated and acts as an oncogene in various cancers; however, its expression, clinical significance, and roles in MDS remain unclear. Here, we found that BC200 was highly expressed in MDS patients compared with normal individuals. Knockdown of BC200 inhibited MDS cell proliferation, colony formation, and cell cycle progression in vitro and suppressed the growth and invasiveness of MDS cells in vivo. Mechanistic investigations revealed that BC200 functioned as a miRNA sponge to positively regulate the expression of MYB through sponging miR-150-5p and subsequently promoted malignant proliferation of MDS cells. Conversely, we found that BC200 was a direct transcriptional target of MYB, and knockdown of MYB abolished the oncogenic effect of BC200/miR-150-5p. Taken together, our results revealed that the BC200/miR-150-5p/MYB positive feedback loop promoted the proliferation of MDS cells and is expected to be a potential biomarker and therapeutic target in MDS.

Rational design of a helical peptide inhibitor targeting c-Myb-KIX interaction.

The transcription factor c-Myb promotes the proliferation of hematopoietic cells by interacting with the KIX domain of CREB-binding protein; however, its aberrant expression causes leukemia. Therefore, inhibitors of the c-Myb-KIX interaction are potentially useful as antitumor drugs. Since the intrinsically disordered transactivation domain (TAD) of c-Myb binds KIX via a conformational selection mechanism where helix formation precedes binding, stabilizing the helical structure of c-Myb TAD is expected to increase the KIX-binding affinity. Here, to develop an inhibitor of the c-Myb-KIX interaction, we designed mutants of the c-Myb TAD peptide fragment where the helical structure is stabilized, based on theoretical predictions using AGADIR. Three of the four initially designed peptides each had a different Lys-to-Arg substitution on the helix surface opposite the KIX-binding interface. Furthermore, the triple mutant with three Lys-to-Arg substitutions, named RRR, showed a high helical propensity and achieved three-fold higher affinity to KIX than the wild-type TAD with a dissociation constant of 80 nM. Moreover, the RRR inhibitor efficiently competed out the c-Myb-KIX interaction. These results suggest that stabilizing the helical structure based on theoretical predictions, especially by conservative Lys-to-Arg substitutions, is a simple and useful strategy for designing helical peptide inhibitors of protein-protein interactions.

C/EBPß sustains the oncogenic program of AML cells by cooperating with MYB and co-activator p300 in a transcriptional module.

Transcription factor MYB is a key regulator of gene expression in hematopoietic cells and has emerged as a novel drug target for acute myeloid leukemia (AML). Studies aiming to identify potential MYB inhibitors have found that the natural compound helenalin acetate (HA) inhibits viability and induces cell death and differentiation of AML cells by disrupting the MYB-induced gene expression program. Interestingly, CCAAT-box/enhancer binding protein ß (C/EBPß), a transcription factor known to cooperate with MYB and the co-activator p300 in myeloid cells, rather than MYB itself, was identified as the primary target of HA. This supports a model in which MYB, C/EBPß, and p300 form the core of a transcriptional module that is essential for maintenance of the proliferative potential of AML cells, highlighting a novel role for C/EBPß as a proleukemogenic factor.

Genome-wide analysis and transcriptional reprogrammings of MYB superfamily revealed positive insights into abiotic stress responses and anthocyanin accumulation in Carthamus tinctorius L.

The MYB transcription factors comprise one of the largest superfamilies in plants that have been implicated in the regulation of plant-specific metabolites and responses to biotic and abiotic stresses. Here, we present the first comprehensive genome-wide analysis and functional characterization of the CtMYB family in Carthamus tinctorius. A total of 272 CtMYBs were identified and classified into 12 subgroups using comparative phylogenetic analysis with Arabidopsis and rice orthologs. The overview of conserved motifs, gene structures, and cis elements as well as the expression pattern of CtMYB genes indicated the diverse roles of these transcription factors during plant growth, regulation of secondary metabolites, and various abiotic stress responses. The subcellular localization and transactivation analysis of four CtMYB proteins indicated predominant localization in the nuclei with enhanced transcriptional activation in yeast. The expression of CtMYB63 induced with various abiotic stress conditions showed upregulation in its transcription level. In addition, the expression analysis of the core structural genes of anthocyanin biosynthetic pathway under drought and cold stress in CtMYB63 overexpressed transgenic lines also supports the notion of CtMYB63 transcriptional reprogramming in response to abiotic stress by upregulating the anthocyanin biosynthesis. Together, our findings revealed the underlying regulatory mechanism of CtMYB TF network involving enhanced cold and drought stress tolerance through activating the rapid biosynthesis of anthocyanin in C. tinctorius. This study also presents useful insights towards the establishment of new strategies for crop improvements.