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Tom Kerppola |
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Professor of Biological Chemistry |
 Kerppola Photo |
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Investigator of the Howard Hughes Medical Research Institute |
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Architecture and dynamics of proto-oncogene transcription factor complexes |
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Ph.D., University of California, Berkeley |
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| Dept: Biological Chemistry | ||||||||
| Office Address: 4570A Medical Science Research Building II | ||||||||
| Phone: (734) 647-4763 | ||||||||
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Email: kerppola@umich.edu |
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| Kerppola Lab Online | ||||||||
| Our
research is directed toward understanding the architecture and dynamics
of transcription regulatory protein complexes. We have developed
several novel methods for analysis of mechanisms of transcriptional
cooperativity. Interactions between proteins that bind to separate
regulatory elements require bending of intervening DNA. We have
discovered a novel mechanism of protein-induced DNA bending mediated by
electrostatic interactions. We are investigating the effect of the
recognition sequence on DNA bending to allow prediction of the DNA
structure in nucleoprotein complexes. Eukaryotic transcription factors often function as heterodimers that recognize palindromic DNA binding sites. The orientation of heterodimer binding to DNA influences interactions with adjacent proteins. We have discovered that Fos-Jun heterodimers bind to different regulatory elements in opposite orientations. We are investigating the determinants of the orientation of heterodimer binding to define the role of binding orientation in transcription activation. Selective control of gene expression requires cooperation among multiple transcription regulatory proteins. The assembly and dynamics of such multi-protein regulatory complexes influences the kinetics and duration of transcription activation. We have determined the rates of assembly and isomerization of the NFAT1-Fos-Jun-ARRE2 complex. We are investigating the factors that determine the stability and transcriptional activity of this complex. Our studies attempt to bridge the gap between the structures of individual transcription factors and the concerted function of multi-protein transcription factor complexes. We wish to understand the architecture of promoter complexes and the principles that underlie transcriptional cooperativity. For further information, see our Howard Hughes Medical Institute web site at http://www.hhmi.org/research/investigators/kerppola.html |
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Representative Publications |
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