Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation.

ABSTRACT:

Rationale

Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear whether this chromatin reader protein functions in cell type-specific manner to control pathological myocardial fibrosis. Furthermore, the molecular mechanisms by which BRD4 stimulates the transcriptional program for cardiac fibrosis remain unknown.

Objective

We sought to test the hypothesis that BRD4 functions in a cell-autonomous and signal-responsive manner to control activation of cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart.

Methods and results

RNA-sequencing, mass spectrometry, and cel

SUBMITTER: Stratton MS 

PROVIDER: S-EPMC7310347 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature