Identification of the transcription factor MAZ as a regulator of erythropoiesis.

Erythropoiesis requires a combination of ubiquitous and tissue-specific transcription factors (TFs). Here, through DNA affinity purification followed by mass spectrometry, we have identified the widely expressed protein MAZ (Myc-associated zinc finger) as a TF that binds to the promoter of the erythroid-specific human α-globin gene. Genome-wide mapping in primary human erythroid cells revealed that MAZ also occupies active promoters as well as GATA1-bound enhancer elements of key erythroid genes. Consistent with an important role during erythropoiesis, knockdown of MAZ reduces α-globin expression in K562 cells and impairs differentiation in primary human erythroid cells. Genetic variants in the MAZ locus are associated with changes in clinically important human erythroid traits. Taken together, these findings reveal the zinc-finger TF MAZ to be a previously unrecognized regulator of the erythroid differentiation program.

Employment and suicidal rates during economic recession: A country-targeted integrative review.

BACKGROUND: The economic crisis' effects on suicide rates for countries undergoing or exiting austerity measures have been widely debated. This integrative review aimed to identify, appraise, and synthesize available evidence of employment status effect on suicide mortality rates in Greece during the recent economic recession period. METHODS: A literature review of studies evaluating suicides in the general Greek population, as well as across age and gender groups, in relation to employment during the economic crisis period was performed. PubMed electronic database was searched for relevant articles published in English or Greek language from 2009 up to February 2020. Appraisal was carried out based on the Hierarchy of Evidence Rating System and the GRADE guidelines. RESULTS: A total of 24 articles met all inclusion criteria with 20 of them at level IV, 2 at level VII, and 2 at level VIII. A total of 18 studies reported increase of suicide rates during the economic recession period. About 12 studies examined the co-relation between unemployment and suicide rate, with ten studies showing a positive correlation. Moreover, thirteen studies reported data on the effect of gender and age variables on suicide rates. CONCLUSION: Evidence shows that suicide mortality rates in Greece increased after the eruption of economic recession, particularly after the implementation of radical austerity measures (2011-2014). This increase was positively correlated with unemployment and was more prominent among males of working age. Further in depth epidemiological research of regional variations in terms of profile and contributing or enabling factors of suicidal behavior is needed.

The role of the polycomb complex in silencing alpha-globin gene expression in nonerythroid cells.

Although much is known about globin gene activation in erythroid cells, relatively little is known about how these genes are silenced in nonerythroid tissues. Here we show that the human alpha- and beta-globin genes are silenced by fundamentally different mechanisms. The alpha-genes, which are surrounded by widely expressed genes in a gene dense region of the genome, are silenced very early in development via recruitment of the Polycomb (PcG) complex. By contrast, the beta-globin genes, which lie in a relatively gene-poor chromosomal region, are not bound by this complex in nonerythroid cells. The PcG complex seems to be recruited to the alpha-cluster by sequences within the CpG islands associated with their promoters; the beta-globin promoters do not lie within such islands. Chromatin associated with the alpha-globin cluster is modified by histone methylation (H3K27me3), and silencing in vivo is mediated by the localized activity of histone deacetylases (HDACs). The repressive (PcG/HDAC) machinery is removed as hematopoietic progenitors differentiate to form erythroid cells. The alpha- and beta-globin genes thus illustrate important, contrasting mechanisms by which cell-specific hematopoietic genes (and tissue-specific genes in general) may be silenced.