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}
}
https://doi.org/10.1016/j.celrep.2016.11.039
Web of Science
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