Fibroblast growth factors (FGFs) prime the limb specific <i>Shh</i> enhancer for chromatin changes that balance histone acetylation mediated by E26 transformation-specific (ETS) factors.

ABSTRACT: Sonic hedgehog (Shh) expression in the limb bud organizing centre called the zone of polarizing activity is regulated by the ZRS enhancer. Here, we examine in mouse and in a mouse limb-derived cell line the dynamic events that activate and restrict the spatial activity of the ZRS. Fibroblast growth factor (FGF) signalling in the distal limb primes the ZRS at early embryonic stages maintaining a poised, but inactive state broadly across the distal limb mesenchyme. The E26 transformation-specific transcription factor, ETV4, which is induced by FGF signalling and acts as a repressor of ZRS activity, interacts with the histone deacetylase HDAC2 and ensures that the poised ZRS remains transcriptionally inactive. Conversely, GABPα, an activator of the ZRS, recruits p300, which is associat

SUBMITTER: Peluso S 

PROVIDER: S-EPMC5659820 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature