BCOR regulates mesenchymal stem cell function by epigenetic mechanisms

Zhipeng Fan, Takayoshi Yamaza, Janice S. Lee, Jinhua Yu, Songlin Wang, Guoping Fan, Songtao Shi, Cun Yu Wang

Research output: Contribution to journalArticle

160 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1002-1009
Number of pages8
JournalNature Cell Biology
Volume11
Issue number8
DOIs
Publication statusPublished - Jul 6 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Fan, Z., Yamaza, T., Lee, J. S., Yu, J., Wang, S., Fan, G., Shi, S., & Wang, C. Y. (2009). BCOR regulates mesenchymal stem cell function by epigenetic mechanisms. Nature Cell Biology, 11(8), 1002-1009. https://doi.org/10.1038/ncb1913