A review of the role of zinc finger proteins on hematopoiesis.

The bone marrow is responsible for producing an incredible number of cells daily in order to maintain blood homeostasis through a process called hematopoiesis. Hematopoiesis is a greatly demanding process and one entirely dependent on complex interactions between the hematopoietic stem cell (HSC) and its surrounding microenvironment. Zinc (Zn2+) is considered an important trace element, playing diverse roles in different tissues and cell types, and zinc finger proteins (ZNF) are proteins that use Zn2+ as a structural cofactor. In this way, the ZNF structure is supported by a Zn2+ that coordinates many possible combinations of cysteine and histidine, with the most common ZNF being of the Cys2His2 (C2H2) type, which forms a family of transcriptional activators that play an important role in different cellular processes such as development, differentiation, and suppression, all of these being essential processes for an adequate hematopoiesis. This review aims to shed light on the relationship between ZNF and the regulation of the hematopoietic tissue. We include works with different designs, including both in vitro and in vivo studies, detailing how ZNF might regulate hematopoiesis.

AtZAT4, a C2H2-Type Zinc Finger Transcription Factor from Arabidopsis thaliana, Is Involved in Pollen and Seed Development.

Pollen plays an essential role in plant fertility by delivering the male gametes to the embryo sac before double fertilization. In several plant species, including Arabidopsis, C2H2-type zinc-finger transcription factors (TFs) have been involved in different stages of pollen development and maturation. ZINC FINGER of Arabidopsis thaliana 4 (AtZAT4) is homologous to such TFs and subcellular localization analysis has revealed that AtZAT4 is located in the nucleus. Moreover, analysis of AtZAT4 expression revealed strong levels of it in flowers and siliques, suggesting a role of the encoded protein in the regulation of genes that are associated with reproductive development. We characterized a T-DNA insertional heterozygous mutant Atzat4 (+/−). The relative gene expression analysis of Atzat4 (+/−) showed significant transcript reductions in flowers and siliques. Furthermore, the Atzat4 (+/−) phenotypic characterization revealed defects in the male germline, showing a reduction in pollen tube germination and elongation. Atzat4 (+/−) presented reduced fertility, characterized by a smaller silique size compared to the wild type (WT), and a lower number of seeds per silique. Additionally, seeds displayed lower viability and germination. Altogether, our data suggest a role for AtZAT4 in fertilization and seed viability, through the regulation of gene expression associated with reproductive development.

Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment.

Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment.

The BBX subfamily IV: additional cogs and sprockets to fine-tune light-dependent development.

Plants depend on light during all phases of its life cycle, and have evolved a complex signaling network to constantly monitor its surroundings. Photomorphogenesis, a process during which the plant reprograms itself in order to dwell life in presence of light is one of the most studied phenomena in plants. Recent mutant analyses using model plant Arabidopsis thaliana and protein interaction assays have unraveled a new set of players, an 8-member subfamily of B-box proteins, known as BBX subfamily IV. For the members of this subfamily, positive (BBX21, BBX22) as well as negative (BBX24) functions have been described for its members, showing a strong association to two major players of the photomorphogenic cascade, HY5 and COP1. The roles of these new BBX regulators are not restricted to photomorphogenesis, but also have functions in other facets of light-dependent development. Therefore this newly identified set of regulators has opened up new insights into the understanding of the fine-tuning of this complex process.

Metallopanstimulin / S27 Ribosomal Antigen Expression in Stages I and II Breast Cancer: its Relationship with Clinicopathologic Factors.

Metallopanstimulin (MPS-1)/S27 ribosomal protein is involved in cellular proliferation and oncogenesis. In this study, we have examined the expression of the MPS-1 protein in 120 stages I and II breast carcinomas to study its relationship with breast cancer prognosis. We also determined if there was any relationship of MPS-1 with other biological markers commonly used in breast cancer prognosis. The expression of MPS-1 protein was analyzed by immunohistochemistry using specific anti-MPS-1 antibodies. We found that there was greater expression of MPS-1 in tumors of greater size and in higher histological grades. Thus, in tumors with more histological aggressiveness there is more MPS-1. Both were frequently associated with a greater proliferative activity. There was also a significant association between the expression of MPS-1 with the expression of receptors for progesterone (p=0.004), estrogens (p=0.03), bcl-2 (p=0.002), and MIB-1 (p=0.03). After univariate logistic regression analysis, we found that overexpression of MPS-1 correlated with Disease Free Survival (DFS) (p=0.039), showing that MPS-1 positivity is associated with a greater incidence of recurrence and/or metastasis. There was no association between overexpression of MPS-1 and poor Overall Survival (OS) (p=0.146). The results presented here indicate a significant correlation between overexpression of MPS-1/S27 ribosomal protein and more aggressive breast cancer growth. These results suggest that the MPS-1 antigen may be a useful marker to understand better the biological behavior of breast cancer.