Pioneer factor Foxa2 enables ligand-dependent activation of type II nuclear receptors FXR and LXRα.

ABSTRACT:

Objective

Type II nuclear hormone receptors, including farnesoid X receptors (FXR), liver X receptors (LXR), and peroxisome proliferator-activated receptors (PPAR), which serve as drug targets for metabolic diseases, are permanently positioned in the nucleus and thought to be bound to DNA regardless of the ligand status. However, recent genome-wide location analysis showed that LXRα and PPARα binding in the liver is largely ligand-dependent. We hypothesized that pioneer factor Foxa2 evicts nucleosomes to enable ligand-dependent binding of type II nuclear receptors and performed genome-wide studies to test this hypothesis.

Methods

ATAC-Seq was used to profile chromatin accessibility; ChIP-Seq was performed to assess transcription factors (Foxa2, FXR, LXRα, and PPARα) binding;

SUBMITTER: Kain J 

PROVIDER: S-EPMC8350412 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature