Chromatin Structure Section

Keji Zhao, PhD, Principle Investigator

Eukaryotic DNA is organized into a highly ordered chromatin structure that ultimately controls the expression potential of a eukaryotic genome. The status of chromatin modification can be mitotically stable and preserves information that determines a cell’s identity. Our research is focused on how the chromatin structure is modified during cellular development and how the modification determines the expression potential of a specific genomic locus using systems biology and molecular biology approaches.

The collection of mitotically stable chromatin modifications in a cell reconstitutes an epigenome, which encodes the information for the expression of a genome. In order to understand the structure and function of the human genomes, we need to define the human epigenomes by mapping the genome-wide patterns of chromatin modifications and distribution of the corresponding enzymes. For this purpose, we have developed an unbiased Genome-wide MApping Technique (GMAT) to analyze the global histone modifications. The method has been successfully used to identify the genome-wide target sites of the histone H3 acetylase GCN5 in yeast. Application of this technique to human T cells has allowed to us discover “histone acetylation islands” as transcriptional and chromatin regulatory elements. The 46,000 acetylation islands in T cells may represent the first experimentally identified regulatory network that mediate T cells development and differentiation. We have also mapped the distribution of H3K4me3 and H3K27me3 in resting human T cells. A surprising discovery from these studies is that the apparently active mark, H3K4me3, and the repressive mark, H3K27me3 are co-localized at thousands of genomic loci. An interactive high-resolution map of these histone modifications is linked to the UCSC genome browser. We are using GMAT to (1) identify patterns of histone modifications in the human genome, (2) to study how the patterns are established; (3) to reveal the relationship between histone modification patterns and gene expression profiles; and (4) to understand diseases resulting from mis-regulation of the epigenetic modifications.

We are also interested in the function of ATP-dependent chromatin remodeling pathway and non-classical Z-DNA structure in genome function.

For postdoctoral training opportunities, please contact Keji Zhao.