Bloomberg Distinguished Professor
Biology Department, School of Arts and Sciences
Molecular Biology and Genetics Department, School of Medicine
RESEARCH OVERVIEW
We are an interdisciplinary team using the tools of biophysics, biochemistry, genetics, molecular and structural biology to elucidate the structure and function of chromatin, the native state of the genome in association with proteins and RNAs. This ‘epigenome’ carries the blueprint of gene expression programs directing cell growth, homeostasis and differentiation throughout plant and animal life. Our basic studies are highly relevant to medicine as genetic mutations and dysfunctions of the epigenome underlie many human diseases.
We are most interested in the role of nucleosome organization and dynamics in controlling gene transcription. Genomes are packaged as arrays of nucleosomes, fundamental histone-DNA particles that are inaccessible to RNA polymerase enzymes that transcribe DNA into RNA, the first step of information flow from genes to proteins. Initiation of transcription requires alterations in nucleosome and chromatin architecture at promoter and enhancer regulatory DNAs, allowing RNA polymerase recruitment and activity at transcription start sites. We seek to elucidate molecular mechanisms underlying this basic process. How do sequence-specific transcription factors operate together with ATP-dependent chromatin remodeling and histone modification enzymes to control transcription on chromatin? We seek answers at the single-molecule level where individual proteins are visualized in real time to decipher their functional behaviors.
Cellular Stress and Cell Signaling | Genetics, Genomics and Gene Regulation
Selected Publications
Tang X, Li T, Liu S, Wisniewski J, Zheng Q, Rong YK, Lavis LD, Wu C. Kinetic Principles Underlying Pioneer Function of GAGA Transcription Factor in Live Cells. Nature Structural & Molecular Biology, 2022.
Carcamo CC, Poyton MF, Ranjan A, Park G, Louder RK, Feng XA, Kim JM, Dzu T, Wu C, Ha T. ATP binding facilitates target search of SWR1 chromatin remodeler by promoting one-dimensional diffusion on DNA. eLife, 2022.
Poyton MF, Feng XA, Ranjan A, Lei Q, Wang F, Zarb JS, Louder RK, Park G, Jo MH, Ye J, Liu S, Ha T and Wu C. Coordinated DNA and Histone Dynamics Drive Accurate Histone H2A.Z Exchange. Science Advances, 2022.
Nguyen VQ, Ranjan A, Liu S, Tang X, Ling YH, Wisniewski J, Mizuguchi G, Li KY, Jou V, Zheng Q, Lavis LD, Lionnet T, Wu C. Spatiotemporal coordination of transcription preinitiation complex assembly in live cells. Molecular Cell, 2021.
Lionnet T, Wu C. Single-molecule tracking of transcription protein dynamics in living cells: seeing is believing, but what are we seeing? Current Opinion in Genetics & Development, 2021.