Michael Bustin, Ph.D.

Michael Bustin is the Chief of the Protein Section in LMC. He obtained his PhD from the University of 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 were he was appointed as an associate professor. He is an adjunct professor in the Department of Biochemistry, Georgetown University. He served on the editorial board of several journals, and received several awards including the Humboldt prize. His research interests center on the role of chromosomal proteins in chromatin function and gene expression.

RESEARCH

Chromosomal Proteins and Chromatin Function: Precise and specific interactions between chromosomal proteins and DNA are key elements for proper packaging of the DNA into chromatin, and are necessary for the  orderly progression of complex processes such as transcription, replication, recombination and repair. Our aim is to understand the molecular mechanisms whereby specific chromosomal proteins affect various DNA-dependent activities in the context of chromatin. Specifically, we study  the chromatin organization and cellular function of histones and HMG proteins. HMG proteins, the most abundant  group of non histone nuclear proteins, serve as architectural elements which affect the structure of both the DNA and the chromatin fiber (Bustin and Reeves, Prog. Nucl. Acid Res. Mol. Biol., 54, 35, 1996). Structural  alterations caused by HMG proteins facilitate a variety of DNA-dependent processes occuring in the context of chromatin. Presently, we focus on the HMG-14/-17 subgroup which are the only nuclear  proteins that bind specifically to nucleosome cores. These proteins unfold chromatin and facilitate access to the nucleosome. Using a variety of biochemical, immunochemical, cell biological and molecular biological approaches we study the structure of the proteins and their genes, the organization of the proteins in nucleosomes, their expression during the cell cycle and differentiation, the manner in which they assemble into the chromatin fiber, the pathway of their entry into the nucleus, their intranuclear trafficking,  and their role in transcription and cellular differentiation. These studies are relevant to the understanding of molecular mechanisms involved in the generation of the chromatin structure of transcriptionally active genes.

 

   

1. Sawchuck, D. J., Weis-Garcia, F., Malik, S., Besmer, E., Roeder, R., Bustin, M., Nussenzweig, M.C. and Cortes, P.: V(D)J recombination: Efect of whole cell extract and DNA bending proteins in 12/33 dependent cleavage. J Exp Med 185:2025-2032, 1997.
2. Weigmann, N., Trieschmann, L. and Bustin, M.: Enhancement of the transcription potential of nascent chromatin by chromosomal proteins HMG-14/-17 is coupled to nucleosome assembly and not DNA synthesis. DNA Cell Biol 16: 1207-1216, 1997.
3. Histone Acetyltransferase Activity of  Human Gcn5 and Pcaf Is Stabilized by Preincubation with Cofactors. J Biol Chem 272:27253-27258, 1997.
4. Ding, H.F., Bustin, M. and Hansen, U.: Alleviation of histone H1-mediated transcriptional repression and chromatin compaction by chromosomal protein  HMG-14. Mol Cell Biol 17:5843-5855, 1997.
5. Postnikov, Y.V.,  Herrera, J.E., Hock, R., Scheer, U and Bustin, M: Clusters of nucleosomes containing chromosomal proteins HMG-17 in chromatin. J Mol Biol 274:454-465, 1997.
6. Bustin, M.: Condensation of research.  Zappavigna, V., Falciola, L., Citterich, M.H., Cavillio,F. and Bianchi, M.E.: HMG-1 interacts with HOX proteins and enhances their DNA binding and transcription activation. Chemtract Biochem Mol Biol 10:117-122, 1997.
7. Vestner, B., Bustin, M. and Gruss, C: Stimulation of replication efficiency of a chromatin template by chromosomal protein HMG-17. J. Biol Chem 273:9409-9414, 1998.
8.  Jayarmann, L., Murthy, K.G.K., Manley, J.L., Bustin, M. and Prives, C.: High Mobility Group protein-1 is a unique activator of p53. Genes Dev 12:462-472, 1998.
9. Trieschmann, L., Martin, B and Bustin, M.: The chromatin unfolding domain of chromosomal protein HMG-14 targets the amino terminal tail of histone H3 in nucleosomes.  Proc Nat Acad Sci 95: 5468-5473, 1998
10. Postnikov , Y.V. and Bustin, M.: Reconstitution of HMG-14/-17 proteins into nucleosomes and chromatin. Methods in Enzymol. (in press)
11. Sakaguchi, K., Herrera, J.E., Saito, S., Bustin, M. Anderson, C.W. and Appella, E.: DNA damage activated p53 through a phosphorylation-acetylation cascade. Genes Dev (in press).

 

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