Identification and detection of mutations potentially associated with decreased susceptibility to macrolides and lincomycin in Mycoplasma anserisalpingitidis isolates.

Mycoplasma anserisalpingitidis infection is associated with the inflammation of the genital tract and cloaca, embryo lethality and decreased egg production in geese, leading to serious economic losses. This bacterium has so far been described in Europe and Asia. There is no commercially available vaccine against M. anserisalpingitidis, thus treatment of waterfowl mycoplasmosis relies mainly on antimicrobial therapy. However, M. anserisalpingitidis isolates with decreased susceptibility to macrolides and lincomycin have been reported before. The minimal inhibitory concentration (MIC) values of tilmicosin, tylosin, tylvalosin and lincomycin were determined against 82 M. anserisalpingitidis isolates originating from Hungary, Poland, China and Vietnam. Whole-genome sequence analyses revealed two mutations in the 23S rRNA coding regions and one mutation in the 50S ribosomal protein L22 coding gene possibly correlating with decreased susceptibility to the examined antibiotics. Mismatch amplification mutation assays coupled with melt analysis (melt-MAMAs) were designed to detect the nucleotide substitutions. This study is the first to describe resistance-related mutations in the goose pathogen M. anserisalpingitidis. The developed molecular assays support targeted antibiotic usage, hence their use may help to reduce the development and spread of antibiotic resistance.

The effect of a light finger touch on the signal complexity during quiet standing.

The purpose of the study was to investigate the influence of additional tactile information (light fingertip touch) on the postural sway and regularity of center-of-pressure (COP) fluctuations. Thirty-two young, healthy participants performed a quiet standing task (30 s) on a force platform with and without light fingertip touch. COP time-series were analyzed using standard postural sway measures (range, root mean square error, velocity), COP regularity was measured with Sample entropy. Participants demonstrated significantly smaller postural sway with a light touch, but only in the anteroposterior direction. The amount of sway with additional tactile information in the sagittal plane reached the level of sway in the frontal plane without this information. Similarly, COP fluctuations were more irregular during light touch condition only in the anteroposterior direction, as evidenced by significantly higher Sample entropy. Furthermore, COP regularity decreased in the sagittal plane and reached level in the frontal plane without light touch. These results suggest that postural sway is mostly controlled in the sagittal plane and that in the mediolateral direction the control is mostly automated. In conclusion, our results support the notion that the light touch provides additional information which enhances postural stabilization. Our results expand the relation between COP regularity and the attention invested in posture in the touch domain and prove that light touch, as an attentional demanding task, leads to increased COP irregularity. Nonlinear measures of signal regularity (i.e., SampEn) provide surplus insight into human postural control and can be used as an additional useful tool to traditional balance measures.

Efficient RNA polymerase II pause release requires U2 snRNP function.

Transcription by RNA polymerase II (Pol II) is coupled to pre-mRNA splicing, but the underlying mechanisms remain poorly understood. Co-transcriptional splicing requires assembly of a functional spliceosome on nascent pre-mRNA, but whether and how this influences Pol II transcription remains unclear. Here we show that inhibition of pre-mRNA branch site recognition by the spliceosome component U2 snRNP leads to a widespread and strong decrease in new RNA synthesis from human genes. Multiomics analysis reveals that inhibition of U2 snRNP function increases the duration of Pol II pausing in the promoter-proximal region, impairs recruitment of the pause release factor P-TEFb, and reduces Pol II elongation velocity at the beginning of genes. Our results indicate that efficient release of paused Pol II into active transcription elongation requires the formation of functional spliceosomes and that eukaryotic mRNA biogenesis relies on positive feedback from the splicing machinery to the transcription machinery.

Transcription activation depends on the length of the RNA polymerase II C-terminal domain.

Eukaryotic RNA polymerase II (Pol II) contains a tail-like, intrinsically disordered carboxy-terminal domain (CTD) comprised of heptad-repeats, that functions in coordination of the transcription cycle and in coupling transcription to co-transcriptional processes. The CTD repeat number varies between species and generally increases with genome size, but the reasons for this are unclear. Here, we show that shortening the CTD in human cells to half of its length does not generally change pre-mRNA synthesis or processing in cells. However, CTD shortening decreases the duration of promoter-proximal Pol II pausing, alters transcription of putative enhancer elements, and delays transcription activation after stimulation of the MAP kinase pathway. We suggest that a long CTD is required for efficient enhancer-dependent recruitment of Pol II to target genes for their rapid activation.

Multilocus sequence typing of the goose pathogen Mycoplasma anserisalpingitidis.

Mycoplasma anserisalpingitidis infection is associated with the inflammation of the genital tract and cloaca, embryo lethality, and decreased egg production in geese, leading to serious economic losses. M. anserisalpingitidis has been detected mainly in Central and Eastern Europe, especially in Hungary, but the pathogen was identified recently in China, predicting it's worldwide occurrence. In this study, a novel multilocus sequence typing (MLST) scheme was developed to analyse phylogenetic relationships between M. anserisalpingitidis field isolates and clinical specimens originating from different geographical locations. Five loci (atpG, fusA, pgiB, plsY, and uvrA) were selected for the final MLST study. The examined 89 M. anserisalpingitidis samples yielded 76 unique sequence types with a 0.994 Simpson's index of diversity. The samples were originated from Hungary, Poland, Ukraine, China, and Vietnam. Phylogenetic analysis revealed the existence of three distinct clades (A-C) and six subclades within clade C. Generally, samples originating from the same geographical locations or livestock integration clustered together. Isolates in clade A showed the closest relationships to the M. anatis outgroup due to sequence similarity of the plsY locus. The highest genetic distance was observed in 5C among the subclades of clade C, containing the Asian and some Hungarian field isolates. The developed MLST assay revealed high diversity of the investigated M. anserisalpingitidis samples. The method proved to be a valuable and cost-effective tool for sequence typing of this waterfowl Mycoplasma species, enabling the better understanding of its phylogeny and providing a robust assay for future molecular epidemiological investigations.

The core genome multi-locus sequence typing of Mycoplasma anserisalpingitidis.

BACKGROUND: Mycoplasma anserisalpingitidis is a waterfowl pathogen that mainly infects geese, can cause significant economic losses and is present worldwide. With the advance of whole genome sequencing technologies, new methods are available for the researchers; one emerging methodology is the core genome Multi-Locus Sequence Typing (cgMLST). The core genome contains a high percentage of the coding DNA sequence (CDS) set of the studied strains. The cgMLST schemas are powerful genotyping tools allowing for the investigation of potential epidemics, and precise and reliable classification of the strains. Although whole genome sequences of M. anserisalpingitidis strains are available, to date, no cgMLST schema has been published for this species. RESULTS: In this study, Illumina short reads of 81 M. anserisalpingitidis strains were used, including samples from Hungary, Poland, Sweden, and China. Draft genomes were assembled with the SPAdes software and analysed with the online available chewBBACA program. User made modifications in the program enabled analysis of mycoplasmas and provided similar results as the conventional SeqSphere+ software. The threshold of the presence of CDS in the strains was set to 93% due to the quality of the draft genomes, resulting in the most accurate and robust schema. Three hundred thirty-one CDSs constituted our cgMLST schema (representing 42,77% of the whole CDS set of M. anserisalpingitidis ATCC BAA-2147), and a Neighbor joining tree was created using the allelic profiles. The correlation was observed between the strains' cgMLST profile and geographical origin; however, strains from the same integration but different locations also showed close relationship. Strains isolated from different tissue samples of the same animal revealed highly similar cgMLST profiles. CONCLUSIONS: The Neighbor joining tree from the cgMLST schema closely resembled the real-life spatial and temporal relationships of the strains. The incongruences between background data and the cgMLST profile in the strains from the same integration can be because of the higher probability of contacts between the flocks. This schema can help with the epidemiological investigation and can be used as a basis for further studies.

Occurrence of Mycoplasma gallisepticum in wild birds: A systematic review and meta-analysis.

Mycoplasma gallisepticum is one of the most important poultry pathogens that can also infect wild birds, but knowledge of potential non-poultry hosts that could be reservoirs of M. gallisepticum is limited. For the paper presented here, we screened three databases (PubMed, Scopus, and the Web of Knowledge) to find articles on the occurrence of M. gallisepticum in different wild bird species that were published between 1951 and 2018. Among 314 studies found, we selected and included 50 original articles that met the pre-established criteria. From those publications we extracted the following information: name of the first author, year of publication, year of sample isolation, country, region, number of birds sampled, number of birds tested by each method, number of positive samples, diagnostic criteria, and if birds were wild or captive. Because different detection techniques were used to confirm the presence of M. gallisepticum in one animal, we decided to perform the meta analyses separately for each method. The estimated prevalence of M. gallisepticum in wild birds was different by each method of detection. Our summary revealed that M. gallisepticum was present in 56 species of bird belonging to 11 different orders, of which 21 species were reported suffering both past and current infection. Our work provides information on wild bird species that could be considered potential reservoirs or carriers of M. gallisepticum and could be helpful to set the direction for future research on the spread and phylogeny of M. gallisepticum in different hosts.

Prevalence and Phylogenetic Analysis of Mycoplasma Synoviae Strains Isolated from Polish Chicken Layer Flocks.

INTRODUCTION: Mycoplasma synoviae (MS) is a chicken pathogen of major economic importance. MATERIAL AND METHODS: Between 2010 and 2016, 906 commercial layer chicken flocks in Poland were examined for MS, and the phylogenetic relationship among the strains was established. Regionally dispersed samples were collected and tested with the use of real-time PCR to detect the 16S-23S intergenic spacer region. Positive samples were also tested with LAMP and conventional PCR to detect the vlhA gene. RESULTS: MS genetic material was detected in 265 (29%) of the tested flocks by real-time PCR, in 227 by the LAMP method and in 202 (22%) by conventional PCR. The by-year percentage of positive samples began at 34% in 2010, rose to 44% in 2012, and declined to 29% in 2016. A phylogenetic analysis of Polish M. synoviae strains using a partial sequence of the vlhA gene showed nine genotypes (A-I), the most frequently occurring being F and C. Pathogenic Polish MS field isolates (n = 27) collected from chickens with clinical signs of infection were grouped for their characteristic symptoms: respiratory for genotypes C, E, F, and I (n = 13), EAA and a drop in laying for genotypes F, E, and C (n = 12), and synovitis for genotype A (n = 2). CONCLUSION: These data showed the country's isolate diversity. The high prevalence suggests the need to introduce appropriate control programmes. This is the first report of molecular epidemiological data on M. synoviae infection in layer chickens in Poland.

Eggshell apex abnormalities caused by two different Mycoplasma synoviae genotypes and evaluation of eggshell anomalies by full-field optical coherence tomography.

BACKGROUND: Mycoplasma synoviae (MS) is an important poultry pathogen worldwide. This bacterium may cause eggshell changes including an altered shell surface, thinning, and increased translucency in different areas, which leads to a greater incidence of eggshell cracks and breaks. In the present study the association between experimental infection of birds with two field strains of MS from different genotypes and the production of abnormal eggs is described. The analysis of those eggshells using a full-field optical coherence tomography (FF OCT) scanner is also reported. RESULTS: Eggshell samples were obtained from three experimental groups of chickens: one control and two infected tracheally with field strains of MS which produced abnormal eggs. In both experimental groups infected with MS a reduction of mean daily egg production by 11% was observed compared to the control group, which started at 21 to 42 dpi. Eggshell apex abnormalities increased to 24.5% of eggs and in some cases, soft-shelled eggs were produced. This study provides the first analysis of shells from anomalous eggs carried out using FF OCT, which allows three-dimensional structural imaging of an investigated sample at micrometre scale. FF OCT showed ultrastructural changes in eggshells and a smaller number of pores on the entire surface of the affected shells. CONCLUSIONS: The eggshell pathology and the concomitant egg production losses that result from infections highlight the economic significance of MS in commercial poultry. There are differences in the strains of MS which may induce eggshell apex abnormalities (EAA) and egg production losses. The use of FF OCT, which is a noninvasive measurement method based on analysis of the light backscattered from the measured object, will confer the ability to control the quality of eggshells in flocks infected with MS.

Clonal chromosomal aberrations in Philadelphia negative cells such as monosomy 7 and trisomy 8 may persist for years with no impact on the long term outcome in patients with chronic myeloid leukemia.

The appearance of clonal chromosomal aberrations in Philadelphia negative cells (CCA/Ph-) during the treatment of chronic myeloid leukemia (CML) was recently confirmed. Importance of these findings has not been clearly defined. We present data on the time of appearance, persistence, size of the CCA/Ph- clone in terms of drugs used and hematological, cytogenetic and molecular response rates. The focus was on the peripheral blood cytopenias and myelodysplastic changes in the bone marrow microscopic evaluation. In 5 out of 155 (3,2%) CML patients, the persistent presence (up to nine years) of CCA/Ph- was found (monosomy 7 and trisomy 8 in unrelated clones in two patients treated with tyrosine kinase inhibitors; trisomy 8 in two patients on imatinib; trisomy 21 in one patient on interferon alfa treatment). Aberrations were present in median 24% Ph- cells in 3-15 subsequent analyses at different cytogenetic and molecular response time points. No evident myelodysplastic changes nor transformation to MDS/AML occurred in patients with CCA/Ph-. All the patients achieved major molecular response (MMR). It seems that CCA/Ph- presence does not affect the long term outcome in patients with chronic myeloid leukemia. Further complex monitoring of the CML patients with CCA/Ph- is still needed.

Micropipette force probe to quantify single-cell force generation: application to T-cell activation.

In response to engagement of surface molecules, cells generate active forces that regulate many cellular processes. Developing tools that permit gathering mechanical and morphological information on these forces is of the utmost importance. Here we describe a new technique, the micropipette force probe, that uses a micropipette as a flexible cantilever that can aspirate at its tip a bead that is coated with molecules of interest and is brought in contact with the cell. This technique simultaneously allows tracking the resulting changes in cell morphology and mechanics as well as measuring the forces generated by the cell. To illustrate the power of this technique, we applied it to the study of human primary T lymphocytes (T-cells). It allowed the fine monitoring of pushing and pulling forces generated by T-cells in response to various activating antibodies and bending stiffness of the micropipette. We further dissected the sequence of mechanical and morphological events occurring during T-cell activation to model force generation and to reveal heterogeneity in the cell population studied. We also report the first measurement of the changes in Young's modulus of T-cells during their activation, showing that T-cells stiffen within the first minutes of the activation process.

MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma.

The main physiological function of MCPIP1 (regnase-1) is negative regulation of inflammation. Moreover, roles of regnase-1 in apoptosis and differentiation have also been described, but its involvement in cancer is yet to be fully recognized. Earlier, we showed a lack of expression of MCPIP1 in both primary tumors and several neuroblastoma cell lines. Additionally, we reported that levels of MCPIP1 and the key neuroblastoma oncoprotein-MYCN were inversely correlated in BE(2)-C clones overexpressing the MCPIP1 gene. Here, we show that exogenous expression of the MCPIP1 protein decreases MYCN mRNA and protein levels without changing the MYCN mRNA half-life. Furthermore, it was shown that MCPIP1-wt exogenous expression affects levels and phosphorylation of MYCN partners such as Aurora A (Thr288), CDC2 (Tyr15 and Thr161), GSK3ß (Ser9), and key cellular components of Akt/mTOR signaling, which regulate MYCN stability and activation. In accordance with the obtained results, we found increased phosphorylation of MYCN protein at Thr58 that causes destabilization of the oncoprotein. Moreover, it is shown that exogenous expression of MCPIP1 does not cause apoptosis. Our data extend knowledge on roles of MCPIP1 in our model and link the protein to regulation of expression and stability of MYCN through decrease of signaling via Akt/mTOR pathway. J. Cell. Biochem. 118: 1741-1755, 2017. © 2016 Wiley Periodicals, Inc.

Influence of enrofloxacin traces in drinking water to doxycycline tissue pharmacokinetics in healthy and infected by Mycoplasma gallisepticum broiler chickens.

Most of antibiotics, administrated in the treatment of poultry diseases are dissolved in drinking water, and it can lead to water supply systems contamination, especially when the regular cleaning is not using. This situation can lead to unconscious administration of low doses of antibiotics to untreated animals. The aim of this study was to clarify the impact of the exposure of enrofloxacin traces (500 µg l(-1)) to doxycycline pharmacokinetics in healthy and experimentally Mycoplasma gallisepticum infected broiler chickens., Two experimental groups, received of enrofloxacin in water and all groups, received 20 mg kg(-1) bw of doxycycline. The compounds concentrations in muscles and livers were determined by LC-MS/MS. The maximum drug tissue concentration (Cmax) of doxycycline was highest in liver obtained from infected chickens which, received enrofloxacin traces (ENR + DC/MG). It was about 40% higher than in healthy chickens from group I which received only doxycycline. It was found that the concentration-time curve AUC(0-t) values in group ENR + DC/MG were almost 75% higher than in the group (DC) and 35% higher than in group (ENR + DC) which also received enrofloxacin traces. The constant exposure of broiler chickens on enrofloxacin traces as well as infection, may significantly influenced on doxycycline tissue pharmacokinetic profile.

Essential Nonredundant Function of the Catalytic Activity of Histone Deacetylase 2 in Mouse Development.

The class I histone deacetylases (HDACs) HDAC1 and HDAC2 play partially redundant roles in the regulation of gene expression and mouse development. As part of multisubunit corepressor complexes, these two deacetylases exhibit both enzymatic and nonenzymatic functions. To examine the impact of the catalytic activities of HDAC1 and HDAC2, we generated knock-in mice expressing catalytically inactive isoforms, which are still incorporated into the HDAC1/HDAC2 corepressor complexes. Surprisingly, heterozygous mice expressing catalytically inactive HDAC2 die within a few hours after birth, while heterozygous HDAC1 mutant mice are indistinguishable from wild-type littermates. Heterozygous HDAC2 mutant mice show an unaltered composition but reduced associated deacetylase activity of corepressor complexes and exhibit a more severe phenotype than HDAC2-null mice. They display changes in brain architecture accompanied by premature expression of the key regulator protein kinase C delta. Our study reveals a dominant negative effect of catalytically inactive HDAC2 on specific corepressor complexes resulting in histone hyperacetylation, transcriptional derepression, and, ultimately, perinatal lethality.

Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids--Synthesis, Characterization, and in Vitro Release Study.

Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent. The structure of the polymeric conjugates was characterized by various spectroscopy techniques. A study of hydrogen nuclear magnetic resonance ((1)H-NMR) and differential scanning calorimetry (DSC) thermodiagrams indicated that the presence of prazosin pendant groups in the macromolecule structures increased the polymer's rigidity alongside increasing glass transition temperature. It has been found that the kinetic release of prazosin from the obtained macromolecular conjugates, tested in vitro under different conditions, is strongly dependent on the physicochemical properties of polymeric matrices. Furthermore, the presence of a urethane bond in the macromolecular conjugates allowed for obtaining a relatively controlled release profile of the drug. The obtained results confirm that the pharmacokinetics of prazosin might be improved through the synthesis of polymeric conjugates containing biomedical polymers and α-amino acids in the macromolecule.

Analysis of genes involved in response to doxorubicin and a GD2 ganglioside-specific 14G2a monoclonal antibody in IMR-32 human neuroblastoma cells.

Neuroblastoma is the most common extra-cranial solid tumor of childhood and it is characterized by the presence of a glycosphingolipid, GD2 ganglioside. Monoclonal antibodies targeting the antigen are currently tested in clinical trials. Additionally, several research groups reported results revealing that ganglioside-specific antibodies can affect cellular signaling and cause direct cytotoxicity against tumor cells. To shed more light on gene expression signatures of tumor cells, we used microarrays to analyze changes of transcriptome in IMR-32 human neuroblastoma cell cultures treated with doxorubicin (DOX) or a mouse monoclonal antibody binding to GD2 ganglioside 14G2a (mAb) for 24 h. The obtained results highlight that disparate cellular pathways are regulated by doxorubicin and 14G2a. Next, we used RT-PCR to verify mRNA levels of selected DOX-responsive genes such as RPS27L, PPM1D, SESN1, CDKN1A, TNFSF10B, and 14G2a-responsive genes such as SVIL, JUN, RASSF6, TLX2, ID1. Then, we applied western blot and analyzed levels of RPS27L, PPM1D, sestrin 1 proteins after DOX-treatment. Additionally, we aimed to measure effects of doxorubicin and topotecan (TPT) and 14G2a on expression of a novel human NDUFAF2 gene encoding for mimitin protein (MYC-induced mitochondrial protein) and correlate it with expression of the MYCN gene. We showed that expression of both genes was concomitantly decreased in the 14G2a-treated IMR-32 cells after 24 h and 48 h. Our results extend knowledge on gene expression profiles after application of DOX and 14G2a in our model and reveal promising candidates for further research aimed at finding novel anti-neuroblastoma targets.

Rapid detection of Mycoplasma synoviae by loop-mediated isothermal amplification.

Mycoplasma synoviae (MS) remains a serious concern in production of poultry and affects world production of chickens and turkeys. Loop-mediated isothermal amplification (LAMP) of DNA has been recently used for the identification of different economically important avian pathogens. The aim of this study was to develop LAMP for simple and inexpensive detection of MS strains in poultry using specifically designed primers targeting hemagglutin A (vlh) gene. The assay was conducted in a water bath for 1 h at 63 °C. The results were visualized after addition of SYBR Green(®) fluorescent dye. LAMP was specific exclusively for MS without cross-reactivity with other Mycoplasma species. The sensitivity of LAMP was determined as 10(-1) CFU/ml and was 1,000 times higher than MS-specific polymerase chain reaction. LAMP assay was conducted on 18 MS field strains to ensure its reliability and usefulness. This is the first report on LAMP development and application for the rapid detection of MS isolated from chickens. This simple method may be applied by diagnostic laboratories without access to expensive equipment.

Physiological and antioxidant responses of two accessions of Arabidopsis thaliana in different light and temperature conditions.

During their lifetime, plants need to adapt to a changing environment, including light and temperature. To understand how these factors influence plant growth, we investigated the physiological and antioxidant responses of two Arabidopsis accessions, Shahdara (Sha) from the Shahdara valley (Tajikistan, Central Asia) in a mountainous area and Lovvik-5 (Lov-5) from northern Sweden to different light and temperature conditions. These accessions originate from different latitudes and have different life strategies, both of which are known to be influenced by light and temperature. We showed that both accessions grew better in high-light and at a lower temperature (16°C) than in low light and at 23°C. Interestingly, Sha had a lower chlorophyll content but more efficient non-photochemical quenching than Lov-5. Sha, also showed a higher expression of vitamin E biosynthetic genes. We did not observe any difference in the antioxidant prenyllipid level under these conditions. Our results suggest that the mechanisms that keep the plastoquinone (PQ)-pool in more oxidized state could play a role in the adaptation of these accessions to their local climatic conditions.

H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.

The selectivity of transcriptional responses to extracellular cues is reflected by the deposition of stimulus-specific chromatin marks. Although histone H3 phosphorylation is a target of numerous signaling pathways, its role in transcriptional regulation remains poorly understood. Here, for the first time, we report a genome-wide analysis of H3S28 phosphorylation in a mammalian system in the context of stress signaling. We found that this mark targets as many as 50% of all stress-induced genes, underlining its importance in signal-induced transcription. By combining ChIP-seq, RNA-seq, and mass spectrometry we identified the factors involved in the biological interpretation of this histone modification. We found that MSK1/2-mediated phosphorylation of H3S28 at stress-responsive promoters contributes to the dissociation of HDAC corepressor complexes and thereby to enhanced local histone acetylation and subsequent transcriptional activation of stress-induced genes. Our data reveal a novel function of the H3S28ph mark in the activation of mammalian genes in response to MAP kinase pathway activation.

Sensing core histone phosphorylation - a matter of perfect timing.

Systematic analysis of histone modifications has revealed a plethora of posttranslational modifications that mediate changes in chromatin structure and gene expression. Histone phosphorylation is a transient histone modification that becomes induced by extracellular signals, DNA damage or entry into mitosis. Importantly, phosphorylation of histone proteins does lead not only to the binding of specific reader proteins but also to changes in the affinity for readers or writers of other histone modifications. This induces a cross-talk between different chromatin modifications that allows the spatio-temporal control of chromatin-associated events. In this review we will summarize the progress in our current knowledge of factors sensing reversible histone phosphorylation in different biological scenarios. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.