Dr. Michelle C. Barton
The University of Texas MD Anderson Cancer Center
Department of Biochemistry and Molecular Biology
Our laboratory is focused on basic mechanisms of regulated and aberrant gene expression during development, tissue regeneration and cancer, especially as dictated by chromatin structure modification and the p53-super family. We are using a combination of in vitro, biochemical approaches and mouse models of p53 function.
Our laboratory developed a dynamic in vitro transcription system assembling cloned DNA templates into chromatin and synthetic nuclei, which actively transport nuclear proteins and progress through S-phase, coupled with chromatin structure and expression analyses. We are using this system and other molecular approaches to investigate p53-mediated control of alpha-fetoprotein (an oncodevelopmental tumor marker) expression, and regulatory disruption during hepatocellular carcinogenesis and liver regeneration.
We make extensive use of chromatin immunoprecipitation (ChIP) assays of cultured cells and solid tissue, such as liver or brain, to determine what transcription factors are bound under specific conditions, what alterations in chromatin they effect and how they dictate a gene’s transcription state. We have used ChIP material to probe micro-arrays of genomic elements (ChIP-on-chip) and determine genomewide distribution of transcription factor interactions with chromatin.
Recently we developed mouse embryonic stem cell lines and mice that express epitope-tagged p53 protein. A TAP (tandem affinity purification) peptide tag was knocked into the genomic locus of p53. We are using this new model system to define p53 protein complexes in specific tissues and during development, tissue regeneration and tumorigenesis.
Denko N, Wernke-Dollries K, Johnson AB, Hammond E, Chiang C-M, and Barton MC. (2003). Hypoxia actively represses transcription by inducing negative cofactor 2 (Dr1/DrAP1) and blocking pre-initiation complex assembly.
J Biol Chem 278, 5744-5749.
Wilkinson DS, Ogden SK, Stratton SA, Piechan JL, Nguyen TT, Smulian GA, and Barton MC. (2005). A direct intersection between p53 and TGF-ß pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol Cell Biol 25, 1200-1212.
Nguyen TT, Cho K, Stratton SA, and Barton MC. (2005). Transcription factor interactions and chromatin modifications associated with p53-mediated, developmental repression of the alpha-fetoprotein gene. Mol Cell Biol 25, 2147-2157.
Cui R, Nguyen TT, Taube J Stratton SA, Feuerman MH, and Barton MC. (2005). Family members p53 and p73 act together in chromatin modification and repression of a-Fetoprotein. J Biol Chem 280, 39152-39160.