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RESEARCH INTERESTS: Gene Regulation/Chromatin Structure and Function/Mammary Gland/Cancer RESEARCH SUMMARY: Our research focuses primarily on the structure and function of eukaryotic chromatin and, more specifically, on the protein-DNA interactions involved in regulation; the transcriptional expression of mammalian genes. For the last several years we have been studying the HMG-I(Y) group of "high mobility" nonhistone chromosomal proteins; founding members of what have now become known as "architectural transcriptional factors" (i.e. proteins that are causally involved in directing the formation of 'stereospecific' DNA-protein complexes on the promoter regions of many mammalian genes in vivo.). By forming such stereospecific promoter complexes, the HMG-I(Y) proteins can regulate, either positively or negtively, gene transcriptional activity in vivo. Both the structure and biochemical/biophysical characteristics of the HMG-I(Y) proteins make them ideal molecules for participating in the formation of multiprotein transcription initiation/repression complexes. For example, HMG-I(Y) proteins are known to recognized DNA structure rather than sequence and bind to the minor groove of AT-rich DNA sequences and also unwind and induce bends in DNA substrates. Furthermore, they have been demonstrated to specifically interact with, and increase the binding affinity of, a number of other known transcription factors. Given these properties, it is perhaps not surprising that increased levels of the HMG-I(Y) proteins have been proposed as diagnostic markers for cancerous transformation and metastatic potential of prostate, thyroid, and breast epithelial cells, and that chromosomal rearrangements have been found in the HMG-I(Y) gene in certain human tumors. Currently, we are continuing our investigations of these important proteins at both the biochemical/biophysical and at the cellular/biological levels.
Dr. Reeves is reading a DMA sequencing gel.
REPRESENTATIVE PUBLICATIONS: Miranda TB, Webb KJ, Edberg DD, Reeves R, Clarke S. 2005 Protein arginine methyltransferase 6 specifically methylates the non-histone chromatin protein HMGA1a. Biochem Biophys Res Commun. 336(3):831-5. Adair JE, Kwon Y, Dement GA, Smerdon MJ, Reeves R. 2005 Inhivition of nucleotide excision repair by high mobility group protein HMGA1. J Biol Chem. 280(37):32184-92. Reeves R, Adair JE. 2005 Role of high mobility group (HMG) chromatin proteins in DNA repair (Amst). 4(8):926-38. De,emt GA, Treff NR, Magnuson NS, Franceschi V, Reeves R. 2005 Dynamic mitochondrial localization of nuclear transcription factor HMGA1. Exp Cell Res. 307(2):388-401. Reeves, R., Beckerbauer, L. 2001. HMGI/Y proteins: flexible regulators of transcription and chromatin structure. Biochim. Biophys. Acta 1519: 13-19.
Banks, G.C., Li, Y. and Reeves, R. (2000) Differential
in vivo modifications of the HMGI(Y) nonhistone chromatin proteins
modulate nucleosome and DNA interactions. Biochem. 39: 833-8346. Reeves, R. and Nissen, M. (1999) purification and assays for high mobility group hmg-i(y) protein function. Meths. Enzymol.304: 155-188. Hill, D., Pedulla, M. and Reeves, R. (1999). directional binding of hmg-i(y) on four-way junction dna and the molecular basis for competitive binding with hmg-1 and histone h1. Nucl. Acids Res. 27: 2135-2144. Banks, G., Mohr, B. and Reeves, R. (1999). the hmg-i(y) at-hook peptide motif confers dna-binding specificity to a structured chimeric protein. J. Biol. Chem. 274: 16536-16544. Bustin M. and R. Reeves (1996). HMG chromosomal proteins: Architectural components that facilitate chromatin function. Prog. Nucl. Acids Res. Molec. Biol. 54:35-100. |
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