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

145 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

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Co-Repressor Proteins
Mesenchymal Stromal Cells
Epigenomics
Mutation
Cuspid
Inborn Genetic Diseases
Adult Stem Cells
Medical Genetics
Gene Silencing
Histones
Cataract
Methylation
Genes
Heart Diseases
Tooth
Homeostasis
Growth

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Fan, Z., Yamaza, T., Lee, J. S., Yu, J., Wang, S., Fan, G., ... 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

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.

In: Nature Cell Biology, Vol. 11, No. 8, 06.07.2009, p. 1002-1009.

Research output: Contribution to journalArticle

Fan, Z, Yamaza, T, Lee, JS, Yu, J, Wang, S, Fan, G, Shi, S & Wang, CY 2009, 'BCOR regulates mesenchymal stem cell function by epigenetic mechanisms', Nature Cell Biology, vol. 11, no. 8, pp. 1002-1009. https://doi.org/10.1038/ncb1913
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. In: Nature Cell Biology. 2009 ; Vol. 11, No. 8. pp. 1002-1009.
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