Associate Professor, Biological Chemistry
B.S., Peking University
Ph.D., University of Rochester
Postdoctoral, The Rockefeller University
Heritable changes in gene expression can occur without changes in DNA sequence. It has emerged that histones, the basic components organizing a eukaryotic genome into hierarchical chromatin structures, are major carriers of epigenetic information. The variation is largely encoded by numerous and often evolutionarily conserved covalent modifications of histones, including methylation, acetylation, phosphorylation and ubiquitinylation. Through histone modifications, chromatin modification enzymes act either synergistically or antagonistically in regulating transcription, cell cycle progression, DNA damage repair, replication development, and differentiation. Given the fundamental roles of histone modifications in organizing chromatin and maintaining proper gene expression patterns, it is not surprising that mutations in chromatin modifying enzymes are often found in human disease.
Our broad objectives are to understand the mechanisms for chromatin modifying enzymes to regulate various cellular processes. Using biochemical approaches and mouse models, we are currently focusing on the regulation of histone H3 lysine 4 methyltransferase MLL and histone acetyltransferase MOF, two enzymes that function coordinately in transcription activation. We are also exploring how disruption of their functions leads to carcinogenesis. Given that MLL deregulation (deletion, amplification and translocation) are found in mix lineage leukemias, a thorough understanding of the mechanism for its action and regulation allows us to develop specific inhibitors as novel chemotherapeutic agents.
2012 Leukemia & Lymphoma Society Scholar Award
2011 Stand Up to Cancer IRG Award
2010 AACR Gertrude B. Elion Cancer Research Award
2010 American Cancer Society RSG Award
2007 Biomedical Science Scholar, University of Michigan
Selected Recent Publications
Y Dou, TA Milne, AJ Tackett, ER Smith, A Fukuda, J Wysocka, CD Allis, BT Chait, JL Hess, RG Roeder (2005). Physical Association and Coordinate Function of the H3 K4 Methyltransferase MLL1 and the H4 K16 Acetyltransferase MOF. Cell 121 (6), 873-85.
J Wysocka, T Swigut, TA Milne, Y Dou, X Zhang, AL Burlingame, RG Roeder, AH Brivanlou, CD Allis (2005). WDR5 Associates with Histone H3 Methylated at K4 and Is Essential for H3 K4 Methylation and Vertebrate Development. Cell 121 (6), 859-72.
Y Dou, TA Milne, AJ Ruthenburg, S Lee, J W Lee, GL Verdine, CD Allis, RG Roeder (2006). Regulation of MLL1 H3 K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 13 (8), 713-719.
4. X Li, L Wu, CAS Corsa, L Wu and Y Dou (2009). Two mammalian MOF complexes regulate transcription activation through distinct mechanisms. Molecular Cell, 36: 290-301.
AJ Ruthenburg, H Li, TA. Milne, S Dewell, RK. McGinty, M Yuen, B Ueberheide, Y Dou, TW Muir, DJ Patel, and CD Allis (2011). BPTF recognizes a mononucleosome-level histone modification pattern via multivalent interactions. Cell, 45(5): 692-706.
L Wu, BM. Zee, Y Wang, BA. Garcia and Y Dou (2011). The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Molecular Cell, 43 (1): 132-144
Y Chen, B Wan, KC. Wang, F Cao, Y Yang, A Protacio, Y Dou, HY. Chang and M Lei (2011). Crystal structure of the N-terminal region of human Ash2L reveals a winged helix motif Involved in DNA Binding. EMBO Rep, 12(8):797-803
H Katoh, ZS Qin, R Liu, L Wang, W Li, X Li, L Wu, R Lyons, Y Dou, P Zheng, Y Liu (2011). FOXP3 activates gene transcription by orchestrating H4K16 acetylation and H3K4 tri-methylation by recruiting MOF and displacing H3K4 demethylase. Molecular Cell, 44 (5): 770-784.
X Li, Li Li, R Pandey, JS. Byun, K Gardner, Z Qin, Y Dou, (2012). The histone acetyltransferase MOF is a key regulator of the embryonic stem cell core transcriptional network. Cell Stem Cell, in press.