Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.

ABSTRACT: Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24-deficient livers share several features, inc

SUBMITTER: Whitton H 

PROVIDER: S-EPMC5946061 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature