The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
BCOR regulates mesenchymal stem cell function by epigenetic mechanisms
Open accessAbstract
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.
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Cites
JmjC-domain-containing proteins and histone demethylation
Klose, R. J., Kallin, E. M., & Zhang, Y. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1945 · Cited by 1,290
JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes
Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., & Pagano, M. (2007) · Nature · doi:10.1038/nature06255 · Cited by 284
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Chang, J., Liu, F., Lee, M., Wu, B., Ting, K., Zara, J. N., Soo, C., Al Hezaimi, K., Zou, W., Chen, X., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300532110 · Cited by 329
Self-citationCellular and molecular mechanisms of tooth root development
Li, J., Parada, C., & Chai, Y. (2017) · Development · doi:10.1242/dev.137216 · Cited by 265
Yang, H., Liang, Y., Cao, Y., Cao, Y., & Fan, Z. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29687 · Cited by 30
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Metadata
- Authors
- Fan, Z., Yamaza, T., Lee, J. S., Yu, J., Wang, S., Fan, G., Shi, S., & Wang, C.-Y.
- Venue
- Nature Cell Biology
- Published
- 2009-07-05
- Volume
- 11
- Issue
- 8
- Pages
- 1002-1009
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2039035015
- Cited by
- 246
- References
- 2
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- green
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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. https://doi.org/10.1038/ncb1913
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