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BCOR regulates mesenchymal stem cell function by epigenetic mechanisms

BCOR (BCL6 co-repressor) represses gene transcription by interacting with BCL-6 1, 2. BCOR mutation is responsible for oculo-facio-cardio-dental (OFCD) syndrome, characterized by canine teeth with extremely long roots, congenital cataracts, craniofacial defects and congenital heart disease3–5. Here...

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Autores principales: Fan, Zhipeng, Yamaza, Takayoshi, Lee, Janice S, Yu, Jinhua, Wang, Songlin, Fan, Guoping, Shi, Songtao, Wang, Cun-Yu
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752141/
https://www.ncbi.nlm.nih.gov/pubmed/19578371
http://dx.doi.org/10.1038/ncb1913
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author Fan, Zhipeng
Yamaza, Takayoshi
Lee, Janice S
Yu, Jinhua
Wang, Songlin
Fan, Guoping
Shi, Songtao
Wang, Cun-Yu
author_facet Fan, Zhipeng
Yamaza, Takayoshi
Lee, Janice S
Yu, Jinhua
Wang, Songlin
Fan, Guoping
Shi, Songtao
Wang, Cun-Yu
author_sort Fan, Zhipeng
collection PubMed
description BCOR (BCL6 co-repressor) represses gene transcription by interacting with BCL-6 1, 2. BCOR mutation is responsible for oculo-facio-cardio-dental (OFCD) syndrome, characterized by canine teeth with extremely long roots, congenital cataracts, craniofacial defects and congenital heart disease3–5. Here we show that BCOR mutation increased osteo/dentinogenic potentials of mesenchymal stem cells (MSCs) isolated from an OFCD patient, providing a molecular explanation for abnormal root growth. AP-2α was identified as a repressive target of BCOR, and BCOR mutation resulted in abnormal activation of AP-2α. Gain- and loss-of-function assays suggested that AP-2α was a key factor that mediated increased osteo/dentinogenic capacity of MSCs. Moreover, we found that BCOR maintained tissue homeostasis and gene silencing by epigenetic mechanisms. BCOR mutation increased histone H3K4/36 methylation in MSCs, thereby reactivating transcription of silenced target genes. In summary, by studying a rare human genetic disease, we unravel an epigenetic mechanism for control of human adult stem cell function.
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spelling pubmed-27521412010-02-01 BCOR regulates mesenchymal stem cell function by epigenetic mechanisms Fan, Zhipeng Yamaza, Takayoshi Lee, Janice S Yu, Jinhua Wang, Songlin Fan, Guoping Shi, Songtao Wang, Cun-Yu Nat Cell Biol Article BCOR (BCL6 co-repressor) represses gene transcription by interacting with BCL-6 1, 2. BCOR mutation is responsible for oculo-facio-cardio-dental (OFCD) syndrome, characterized by canine teeth with extremely long roots, congenital cataracts, craniofacial defects and congenital heart disease3–5. Here we show that BCOR mutation increased osteo/dentinogenic potentials of mesenchymal stem cells (MSCs) isolated from an OFCD patient, providing a molecular explanation for abnormal root growth. AP-2α was identified as a repressive target of BCOR, and BCOR mutation resulted in abnormal activation of AP-2α. Gain- and loss-of-function assays suggested that AP-2α was a key factor that mediated increased osteo/dentinogenic capacity of MSCs. Moreover, we found that BCOR maintained tissue homeostasis and gene silencing by epigenetic mechanisms. BCOR mutation increased histone H3K4/36 methylation in MSCs, thereby reactivating transcription of silenced target genes. In summary, by studying a rare human genetic disease, we unravel an epigenetic mechanism for control of human adult stem cell function. 2009-07-05 2009-08 /pmc/articles/PMC2752141/ /pubmed/19578371 http://dx.doi.org/10.1038/ncb1913 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Fan, Zhipeng
Yamaza, Takayoshi
Lee, Janice S
Yu, Jinhua
Wang, Songlin
Fan, Guoping
Shi, Songtao
Wang, Cun-Yu
BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title_full BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title_fullStr BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title_full_unstemmed BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title_short BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
title_sort bcor regulates mesenchymal stem cell function by epigenetic mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752141/
https://www.ncbi.nlm.nih.gov/pubmed/19578371
http://dx.doi.org/10.1038/ncb1913
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