Michael Bustin, Ph.D. is head of the Protein Section, Laboratory of Metabolism, CCR, NCI. Dr. Bustin received his Ph.D. from University at California, Berkeley and did postdoctoral work in the area of protein chemistry, in the laboratory of Drs. S. Moore and W. Stein at the Rockefeller University in New York, and in the area of immunochemistry at the Weizmann Institute of Science, Israel, where he produced antibodies to histones and pioneered their use for studies on chromatin structure and function. His research interests center on the role of chromosomal proteins in chromatin function, gene expression, development and cancer.
Chromosomal Proteins and Chromatin Function
The precise and specific biding of nuclear proteins to nucleosomes modulates chromatin dynamics and epigenetic regulatory mechanisms and plays a key role in regulating the fidelity of gene expression, the maintenance of genomic stability and the orderly progression of the cell cycle and differentiation. We aim to understand the molecular mechanisms whereby specific chromosomal proteins regulate chromatin function and affect the cellular phenotype. Specifically, we study the chromatin organization and cellular function of HMG proteins, one of the most abundant group of non-histone nuclear proteins, which serve as architectural elements that affect the structure and function of the chromatin fiber. HMG proteins modulate DNA-dependent processes occurring in the context of chromatin, including transcription. Presently, we are focusing on the HMGNs, a family of proteins that bind specifically to nucleosome cores (i.e., to the building block of the chromatin fiber). HMGN proteins affect the structure of the chromatin fiber and the levels of histone modifications thereby playing a role in epigenetic regulation. We are using a multidisciplinary approach that includes the generation and analysis of genetically altered mice, molecular biology, biochemistry and cell biology to study the structure of these proteins, their genome wide organization in chromatin, their precise location on nucleosomes, their expression during the cell cycle and differentiation, the manner in which they assemble into the chromatin fiber, their role in transcription regulation, and their biological function.