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Title: Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13

The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13–/–; Hoxd13–/– limbs. Our results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [4] ;  [5] ;  [5] ;  [6] ;  [7] ;  [8]
  1. Institute de Recherches Cliniques de Montreal (IRCM), Montreal, QC (Canada)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. McGill Univ., Montreal, QC (Canada)
  4. Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC (Canada)
  5. Shriners Hospital for Children, Portland, OR (United States)
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States)
  7. Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC (Canada); Univ. de Montreal, Montreal, QC (Canada)
  8. Institute de Recherches Cliniques de Montreal (IRCM), Montreal, QC (Canada); Univ. de Montreal, Montreal, QC (Canada)
Publication Date:
Grant/Contract Number:
AC02-05CH11231
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 17; Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HOX; transcriptional regulation; limb development; ChIP-seq; chromatin state; enhancer; Histone marks; digit; Hoxa13; Hoxd13
OSTI Identifier:
1378293
Alternate Identifier(s):
OSTI ID: 1393095