Assistant Professor, Harvard Medical School
Ph.D., Molecular and Cell Biology, University of California, Berkeley
B.A., Molecular and Cell Biology, University of California, Berkeley
We study key transcriptional and other gene regulatory events that lead to the acquisition and maintenance of pluripotency in embryonic stem cells (ESCs). ESCs can self-renew or differentiate to produce most of the cells of the body. These distinct but developmentally relevant cell fates are defined by their unique gene expression signatures. Proper execution of these developmental programs requires the precise tuning of gene expression by transcription factors, coactivators and corepressors. Indeed, aberrant transcriptional regulation is the root of many human diseases including developmental disorders, cancers and degenerative diseases.
We have devised various strategies to isolate critical cellular machinery responsible for transcription and to reconstruct the complex process of gene activation in vitro. This technique, in combination with in vivo systems, provides powerful tools to dissect the molecular mechanisms of pluripotency and self-renewal of ESCs, lineage commitment during ESC differentiation, cellular reprogramming, and diseases at the transcriptional level.
We are in the process of characterizing the in vitro biochemical activities and in vivo functions of three newly identified coactivators essential for transcriptional activation by key stem cell-specific transcription factors OCT4 and SOX2. A deeper understanding of the full repertoire of transcription factors operating in stem cells is critical to realizing the full potential of stem cells in tissue regeneration and replacement therapy.
Zhang ET, He Y, Grob P, Fong YW, Nogales E and Tjian R. Architecture of the human XPC DNA repair and stem cell coactivator complex. Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14817-22. doi: 10.1073/pnas.1520104112. Epub 2015 Nov 16. View in Pubmed
Poggioli T, Vujic A, Yang P, Macias-Trevino C, Uygur AN, Loffredo FS, Pancoast JR, Cho M, Goldstein J, Tandias RM, Gonzalez E, Walker RG, Thompson TB, Wagers AJ, Fong YW and Lee RT. Circulating Growth Differentiation Factor 11/8 levels decline with age. Circ Res 2015; doi:10.1161/CIRCRESAHA. 115.307521. View in Pubmed
Cattoglio C, Zhang ET, Grubisic I, Chiba K, Fong YW and Tjian R. Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells. Proc Natl Acad Sci U S A. 2015 May 5;112(18):E2317-26. View in Pubmed
Fong YW, Ho JJ, Inouye C and Tjian R. The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells. eLife 2014 Nov 19;3. View in Pubmed
Fong YW, Cattoglio C and Tjian R. The Intertwined roles of transcription and repair proteins. Mol Cell 2013; 52: 291-302. View in Pubmed
Fong YW, Cattoglio C, Yamaguchi T and Tjian R. Transcriptional regulation by coactivators in embryonic stem cells. Trends Cell Biol 2012; 6: 292-8. View in Pubmed
Fong YW, Inouye C, Yamaguchi T, Cattoglio C, Grubisic I and Tjian R. A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell 2011; 147: 120-31. View in Pubmed
Fong YW and Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 2001; 414: 929-33. View in Pubmed
Fong YW and Zhou Q. Relief of two built-in autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol 2000; 16: 5897-907. View in Pubmed
O’Keeffe B, Fong Y, Chen D, Zhou S and Zhou Q. Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated Tat stimulation of HIV-1 transcription. J Biol Chem 2000; 275: 279-87. View in Pubmed
Chen D, Fong Y and Zhou Q. Specific interaction of Tat with the human but not rodent P-TEFb complex mediates the species-specific Tat activation of HIV-1 transcription. Proc Natl Acad Sci USA 1999; 96: 2728-33. View in Pubmed
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