ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis.

ABSTRACT: ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin^-cKit⁺ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A

SUBMITTER: Li Z 

PROVIDER: S-EPMC5249256 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature