Carl Wu

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.