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Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells

BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with...

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Autores principales: Yan, Jizhou, Chen, Ya-Xiong, Desmond, Angela, Silva, Albert, Yang, Yuqing, Wang, Haoren, Hua, Xianxin
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762371/
https://www.ncbi.nlm.nih.gov/pubmed/17183676
http://dx.doi.org/10.1371/journal.pone.0000047
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author Yan, Jizhou
Chen, Ya-Xiong
Desmond, Angela
Silva, Albert
Yang, Yuqing
Wang, Haoren
Hua, Xianxin
author_facet Yan, Jizhou
Chen, Ya-Xiong
Desmond, Angela
Silva, Albert
Yang, Yuqing
Wang, Haoren
Hua, Xianxin
author_sort Yan, Jizhou
collection PubMed
description BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells.
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spelling pubmed-17623712007-01-04 Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells Yan, Jizhou Chen, Ya-Xiong Desmond, Angela Silva, Albert Yang, Yuqing Wang, Haoren Hua, Xianxin PLoS One Research Article BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells. Public Library of Science 2006-12-20 /pmc/articles/PMC1762371/ /pubmed/17183676 http://dx.doi.org/10.1371/journal.pone.0000047 Text en Yan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yan, Jizhou
Chen, Ya-Xiong
Desmond, Angela
Silva, Albert
Yang, Yuqing
Wang, Haoren
Hua, Xianxin
Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title_full Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title_fullStr Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title_full_unstemmed Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title_short Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells
title_sort cdx4 and menin co-regulate hoxa9 expression in hematopoietic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762371/
https://www.ncbi.nlm.nih.gov/pubmed/17183676
http://dx.doi.org/10.1371/journal.pone.0000047
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