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Transcription Factor Binding Site Analysis Identifies FOXO Transcription Factors as Regulators of the Cutaneous Wound Healing Process.

Roupé, Karl Markus; Veerla, Srinivas LU ; Olson, Joshua; Stone, Erica L; Sørensen, Ole E LU ; Hedrick, Stephen M and Nizet, Victor (2014) In PLoS ONE 9(2).
Abstract
The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors... (More)
The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors during wound healing in vivo in both human and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin was observed, with FOXO3 having the highest expression level in non wounded skin. Impaired re-epithelialization was found in cultures of primary human keratinocytes expressing a constitutively active variant of FOXO3. Conversely knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo mouse model with FOXO3 knockout mice we detected significantly accelerated wound healing. This article illustrates that the proposed approach is a viable method for identifying important regulators of complex biological processes using in vivo samples. FOXO3 has not previously been implicated as an important regulator of wound healing and its exact function in this process calls for further investigation. (Less)
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Contribution to journal
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published
subject
in
PLoS ONE
volume
9
issue
2
publisher
Public Library of Science
external identifiers
  • pmid:24586650
  • wos:000331711900120
  • scopus:84895858633
ISSN
1932-6203
DOI
10.1371/journal.pone.0089274
language
English
LU publication?
yes
id
ce76364c-4fa5-4a72-9fe5-ba1648af2845 (old id 4384146)
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http://www.ncbi.nlm.nih.gov/pubmed/24586650?dopt=Abstract
date added to LUP
2014-04-01 19:00:43
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2017-08-27 04:33:46
@article{ce76364c-4fa5-4a72-9fe5-ba1648af2845,
  abstract     = {The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors during wound healing in vivo in both human and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin was observed, with FOXO3 having the highest expression level in non wounded skin. Impaired re-epithelialization was found in cultures of primary human keratinocytes expressing a constitutively active variant of FOXO3. Conversely knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo mouse model with FOXO3 knockout mice we detected significantly accelerated wound healing. This article illustrates that the proposed approach is a viable method for identifying important regulators of complex biological processes using in vivo samples. FOXO3 has not previously been implicated as an important regulator of wound healing and its exact function in this process calls for further investigation.},
  articleno    = {e89274},
  author       = {Roupé, Karl Markus and Veerla, Srinivas and Olson, Joshua and Stone, Erica L and Sørensen, Ole E and Hedrick, Stephen M and Nizet, Victor},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Transcription Factor Binding Site Analysis Identifies FOXO Transcription Factors as Regulators of the Cutaneous Wound Healing Process.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0089274},
  volume       = {9},
  year         = {2014},
}