Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis [ATAC-Seq]

ABSTRACT: Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation, however cohesin-mutant leukemias do not show genomic instability. We hypothesized reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Bi-allelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation, and revealed an absolute requirement for cohesin in hematopoietic stem cell function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo including competitive transplantation. Smc3 haploinsufficiency red

ORGANISM(S): Mus musculus

SUBMITTER: James Bradner 

PROVIDER: E-GEOD-73215 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress