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Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation

Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited know...

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Autores principales: Gao, Jie, Wang, Jie, Wang, Yumei, Dai, Wei, Lu, Luo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113856/
https://www.ncbi.nlm.nih.gov/pubmed/21695148
http://dx.doi.org/10.1371/journal.pone.0020954
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author Gao, Jie
Wang, Jie
Wang, Yumei
Dai, Wei
Lu, Luo
author_facet Gao, Jie
Wang, Jie
Wang, Yumei
Dai, Wei
Lu, Luo
author_sort Gao, Jie
collection PubMed
description Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively.
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spelling pubmed-31138562011-06-21 Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation Gao, Jie Wang, Jie Wang, Yumei Dai, Wei Lu, Luo PLoS One Research Article Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively. Public Library of Science 2011-06-13 /pmc/articles/PMC3113856/ /pubmed/21695148 http://dx.doi.org/10.1371/journal.pone.0020954 Text en Gao 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
Gao, Jie
Wang, Jie
Wang, Yumei
Dai, Wei
Lu, Luo
Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title_full Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title_fullStr Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title_full_unstemmed Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title_short Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation
title_sort regulation of pax6 by ctcf during induction of mouse es cell differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113856/
https://www.ncbi.nlm.nih.gov/pubmed/21695148
http://dx.doi.org/10.1371/journal.pone.0020954
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