A cohesin cancer mutation reveals a role for the hinge domain in genome organization and gene expression.

ABSTRACT: The cohesin complex spatially organizes interphase chromatin by bringing distal genomic loci into close physical proximity, looping out the intervening DNA. Mutation of cohesin complex subunits is observed in cancer and developmental disorders, but the mechanisms through which these mutations may contribute to disease remain poorly understood. Here, we investigate a recurrent missense mutation to the hinge domain of the cohesin subunit SMC1A, observed in acute myeloid leukemia. Engineering this mutation into murine embryonic stem cells caused widespread changes in gene expression, including dysregulation of the pluripotency gene expression program. This mutation reduced cohesin levels at promoters and enhancers, decreased DNA loops and interactions across short genomic distances, and weake

SUBMITTER: Carico ZM 

PROVIDER: S-EPMC7990204 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature