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This content will become publicly available on November 10, 2015

Title: HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme

The genetic networks that govern vertebrate development are well studied, but how the interactions of trans-acting factors with cis-regulatory modules (CRMs) are integrated into spatiotemporal regulation of gene expression is not clear. The transcriptional regulator HAND2 is required during limb, heart, and branchial arch development. Here, we identify the genomic regions enriched in HAND2 chromatin complexes from mouse embryos and limb buds. Then we analyze the HAND2 target CRMs in the genomic landscapes encoding transcriptional regulators required in early limb buds. HAND2 controls the expression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior and posterior polarity of the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expression. TBX3 is required downstream of HAND2 to refine the posterior Gli3 expression boundary. In conclusion, our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling.
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [4] ;  [4] ;  [5] ;  [5] ;  [3] ;  [6] ;  [1] ;  [1]
  1. Univ. of Basel (Switzerland)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of Amsterdam (Netherlands)
  4. Federal Inst. of Technology Zurich, Basel (Switzerland)
  5. Genentech, Inc., South San Francisco, CA (United States). Dept. of Molecular Biology
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Inst., Walnut Creek, CA (United States)
Publication Date:
OSTI Identifier:
1225559
Grant/Contract Number:
AC02-05CH11231
Type:
Published Article
Journal Name:
Developmental Cell
Additional Journal Information:
Journal Volume: 31; Journal Issue: 3; Journal ID: ISSN 1534-5807
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES