Epigenomic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid Journal Article
| Authors: | Kashyap, V.; Gudas, L. J.; Brenet, F.; Funk, P.; Viale, A.; Scandura, J. M. |
| Article Title: | Epigenomic reorganization of the clustered Hox genes in embryonic stem cells induced by retinoic acid |
| Abstract: | Retinoic acid (RA) regulates clustered Hox gene expression during embryogenesis and is required to establish the anterior-posterior body plan. Using mutant embryonic stem cell lines deficient in the RA receptor γ (RARγ) or Hoxa1 3′-RA-responsive element, we studied the kinetics of transcriptional and epigenomic patterning responses to RA. RARγ is essential for RA-induced Hox transcriptional activation, and deletion of its binding site in the Hoxa1 enhancer attenuates transcriptional and epigenomic activation of both Hoxa and Hoxb gene clusters. The kinetics of epigenomic reorganization demonstrate that complete erasure of the polycomb repressive mark H3K27me3 is not necessary to initiate Hox transcription. RARγ is not required to establish the bivalent character of Hox clusters, but RA/RARγ signaling is necessary to erase H3K27me3 from activated Hox genes during embryonic stem cell differentiation. Highly coordinated, long range epigenetic Hox cluster reorganization is closely linked to transcriptional activation and is triggered by RARγ located at the Hoxa1 3′-RA-responsive element. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; unclassified drug; gene cluster; gene deletion; nonhuman; protein function; animal cell; mouse; genes; cell growth; embryo; embryonic stem cell; transcription factor; cell differentiation; transcription regulation; cell culture; epigenetics; histone h3; transcription; stem cells; embryonic stem cells; binding site; cell stimulation; dna responsive element; retinoic acid; gene location; cell mutant; polycomb group protein; enhancer region; anterior posteriors; body plan; gene clusters; hox gene; long range; polycomb; retinoic acids; transcriptional activations; retinoic acid receptor gamma; transcription factor hoxa1; hoxa gene; hoxb gene |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 286 |
| Issue: | 5 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2011-02-04 |
| Start Page: | 3250 |
| End Page: | 3260 |
| Language: | English |
| DOI: | 10.1074/jbc.M110.157545 |
| PUBMED: | 21087926 |
| PROVIDER: | scopus |
| PMCID: | PMC3030330 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: JBCHA" - "Source: Scopus" |
