The research of the Zhou laboratory is centered on understanding the molecular mechanisms of epigenetic regulation of gene transcription in human biology of health and disease. Stem cell biology is an active area of research in the lab. We specifically seek new structural and functional insights into molecular interactions and regulation of histone-directed gene transcription that governs stem cell self-renewal and lineage commitment. We focus on the roles of the Trithorax (Trx) protein complexes and the Polycomb repressive complexes (PRCs) in gene activation and silencing to attain both mechanistic insight and rational design of small-molecule probes capable of modulating the cellular functions of these transcriptional proteins.
Mujtaba S, Manzur KL, Gurnon JR, Kang M, Van Etten JL, Zhou MM. Epigenetic transcriptional repression of cellular genes by a viral SET protein. Nat Cell Biol. 2008 Sep;10(9):1114-22.
Zeng L, Yap KL, Ivanov AV, Wang X, Mujtaba S, Plotnikova O, Rauscher FJ 3rd, Zhou MM. Structural insights into human KAP1 PHD finger-bromodomain and its role in gene silencing. Nat Struct Mol Biol. 2008 Jun;15(6):626-33.
Ivanov AV, Peng H, Yurchenko V, Yap KL, Negorev DG, Schultz DC, Psulkowski E, Fredericks WJ, White DE, Maul GG, Sadofsky MJ, Zhou MM, Rauscher FJ 3rd. PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell. 2007 Dec 14;28(5):823-37.
Sachchidanand, Resnick-Silverman L, Yan S, Mutjaba S, Liu WJ, Zeng L, Manfredi JJ, Zhou MM. Target structure-based discovery of small molecules that block human p53 and CREB binding protein association. Chem Biol. 2006 Jan;13(1):81-90.
Qian C, Zhang Q, Li S, Zeng L, Walsh MJ, Zhou MM. Structure and chromosomal DNA binding of the SWIRM domain. Nat Struct Mol Biol. 2005 Dec;12(12):1078-85.