Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies Journal Article
| Authors: | Sasca, D.; Yun, H.; Giotopoulos, G.; Szybinski, J.; Evan, T.; Wilson, N. K.; Gerstung, M.; Gallipoli, P.; Green, A. R.; Hills, R.; Russell, N.; Osborne, C. S.; Papaemmanuil, E.; Göttgens, B.; Campbell, P.; Huntly, B. J. P. |
| Article Title: | Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies |
| Abstract: | Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid leukemia and myelodysplastic syndrome patient samples, these data suggest cohesin-mediated alleviation of Etv6 repression is required for dynamic expression at critical erythroid genes during differentiation and how this may be perturbed in myeloid malignancies. © 2019 by The American Society of Hematology. |
| Keywords: | unclassified drug; human cell; promoter region; flow cytometry; cohesin; actin; gene expression; erythropoiesis; protein; cell differentiation; myelodysplastic syndrome; chromatin; histone h3; western blotting; hematopoiesis; upregulation; hematopoietic stem cell; stat5 protein; transcription factor etv6; transcription factor runx1; acute myeloid leukemia; myelopoiesis; histone acetylation; human; priority journal; article; stem cell self-renewal; rad21 protein; stag2 protein; epo receptor |
| Journal Title: | Blood |
| Volume: | 134 |
| Issue: | 24 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2019-12-12 |
| Start Page: | 2195 |
| End Page: | 2208 |
| Language: | English |
| DOI: | 10.1182/blood.2019001553 |
| PUBMED: | 31515253 |
| PROVIDER: | scopus |
| PMCID: | PMC7484777 |
| DOI/URL: | |
| Notes: | Source: Scopus |
