Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782172276548960256 |
---|---|
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. |
format | Text |
id | pubmed-2752141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fanzhipeng bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT yamazatakayoshi bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT leejanices bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT yujinhua bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT wangsonglin bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT fanguoping bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT shisongtao bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms AT wangcunyu bcorregulatesmesenchymalstemcellfunctionbyepigeneticmechanisms |