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

Abstract

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:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1378293
Alternate Identifier(s):
OSTI ID: 1393095
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Name: Cell Reports Journal Volume: 17 Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HOX; transcriptional regulation; limb development; ChIP-seq; chromatin state; enhancer; Histone marks; digit; Hoxa13; Hoxd13

Citation Formats

Sheth, Rushikesh, Barozzi, Iros, Langlais, David, Osterwalder, Marco, Nemec, Stephen, Carlson, Hanqian L., Stadler, H. Scott, Visel, Axel, Drouin, Jacques, and Kmita, Marie. Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13. Netherlands: N. p., 2016. Web. doi:10.1016/j.celrep.2016.11.039.
Sheth, Rushikesh, Barozzi, Iros, Langlais, David, Osterwalder, Marco, Nemec, Stephen, Carlson, Hanqian L., Stadler, H. Scott, Visel, Axel, Drouin, Jacques, & Kmita, Marie. Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13. Netherlands. https://doi.org/10.1016/j.celrep.2016.11.039
Sheth, Rushikesh, Barozzi, Iros, Langlais, David, Osterwalder, Marco, Nemec, Stephen, Carlson, Hanqian L., Stadler, H. Scott, Visel, Axel, Drouin, Jacques, and Kmita, Marie. Thu . "Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13". Netherlands. https://doi.org/10.1016/j.celrep.2016.11.039.
@article{osti_1378293,
title = {Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13},
author = {Sheth, Rushikesh and Barozzi, Iros and Langlais, David and Osterwalder, Marco and Nemec, Stephen and Carlson, Hanqian L. and Stadler, H. Scott and Visel, Axel and Drouin, Jacques and Kmita, Marie},
abstractNote = {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.},
doi = {10.1016/j.celrep.2016.11.039},
journal = {Cell Reports},
number = 11,
volume = 17,
place = {Netherlands},
year = {Thu Dec 01 00:00:00 EST 2016},
month = {Thu Dec 01 00:00:00 EST 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.celrep.2016.11.039

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Cited by: 44 works
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Works referencing / citing this record:

Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes
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  • DOI: 10.1111/dgd.12601

Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development
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Regulatory integration of Hox factor activity with T-box factors in limb development
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  • Jain, Deepak; Nemec, Stephen; Luxey, Maëva
  • Development, Vol. 145, Issue 6
  • DOI: 10.1242/dev.159830

Similarities and differences in the regulation of HoxD genes during chick and mouse limb development
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  • Yakushiji-Kaminatsui, Nayuta; Lopez-Delisle, Lucille; Bolt, Christopher Chase
  • PLOS Biology, Vol. 16, Issue 11
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