GATA2 decommissioning of enhancers: A mechanism to constrain inflammatory signaling.

ABSTRACT: GATA2 establishes transcriptomes governing hematopoietic stem/progenitor cell development. In progenitors, GATA2 represses inflammatory genes (Il6st and Il6ra) encoding IL6ST/GP130 and IL6RA receptor subunits mediating IL-6 signaling. While IL6ST heterodimerizes with IL6RA, IL-11, IL-27, oncostatin M, and leukemia inhibitory factor receptors, IL6RA heterodimerizes exclusively with IL6ST to confer IL-6 signaling. As GATA2-dependent repression is not well understood, we devised a multi-omics strategy to elucidate mechanisms underlying repression and applied the approach to the cytokine/chemokine receptor gene family. Identifying accessible distal and intronic chromatin sites in GATA2-deficient (GATA2^low), but not wild-type, progenitors unveiled that GATA2 represses Il6st and Il6ra

SUBMITTER: Jung MM 

PROVIDER: S-EPMC12580906 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature