Dual role of Brg chromatin remodeling factor in Sonic hedgehog signaling during neural development

Xiaoming Zhan, Xuanming Shi, Zilai Zhang, Yu Chen, Jiang I. Wu

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Sonic hedgehog (Shh) signaling plays diverse roles during animal development and adult tissue homeostasis through differential regulation of Gli family transcription factors. Dysregulated Shh signaling activities have been linked to birth defects and tumorigenesis. Here we report that Brg, an ATP-dependent chromatin remodeling factor, has dual functions in regulating Shh target gene expression. Using a Brg conditional deletion in Shh-responding neural progenitors and fibroblasts, we demonstrate that Brg is required both for repression of the basal expression and for the activation of signal-induced transcription of Shh target genes. In developing telencephalons deficient for Brg, Shh target genes were derepressed, whereas Brg-deleted cerebellar granule neuron precursors failed to respond to Shh to increase their proliferation. The repressor function of Brg was mediated through Gli3 and both the repressor and activator functions of Brg appeared to be independent of its ATPase activity. Furthermore, Brg facilitates Gli coactivator histone deacetylase (HDAC) binding to the regulatory regions of Shh target genes, providing a possible mechanism for its positive role in Shh signaling. Our results thus reveal that a complex chromatin regulation mechanism underlies the precise transcription outcomes of Shh signaling and its diverse roles during development.

Original languageEnglish (US)
Pages (from-to)12758-12763
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011

Keywords

  • Gli proteins
  • Neural development
  • SWI/SNF complexes
  • Signal transduction
  • Transcription regulation

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Dual role of Brg chromatin remodeling factor in Sonic hedgehog signaling during neural development'. Together they form a unique fingerprint.

  • Cite this