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- Title
BCOR regulates mesenchymal stem cell function by epigenetic mechanisms.
- Authors
Zhipeng Fan; Yamaza, Takayoshi; Lee, Janice S.; Jinhua Yu; Songlin Wang; Guoping Fan; Songtao Shi; Cun-Yu Wang
- Abstract
The BCL-6 co-repressor (BCOR) represses gene transcription by interacting with BCL-6 (Refs 1, 2). BCOR mutation is responsible for oculo-facio-cardio-dental (OFCD) syndrome, which is characterized by canine teeth with extremely long roots, congenital cataracts, craniofacial defects and congenital heart disease. Here we show that BCOR mutation increased the osteo-dentinogenic potential of mesenchymal stem cells (MSCs) isolated from a patient with OFCD, 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 suggest that AP-2α is a key factor that mediates the increased osteo-dentinogenic capacity of MSCs. Moreover, we found that BCOR maintained tissue homeostasis and gene silencing through epigenetic mechanisms. BCOR mutation increased histone H3K4 and H3K36 methylation in MSCs, thereby reactivating transcription of silenced target genes. By studying a rare human genetic disease, we have unravelled an epigenetic mechanism for control of human adult stem cell function.
- Publication
Nature Cell Biology, 2009, Vol 11, Issue 8, p1002
- ISSN
1465-7392
- Publication type
Academic Journal
- DOI
10.1038/ncb1913