Daniel A. Bochar, Ph.D.
Assistant Professor, Biological Chemistry
B.S., University of Illinois
Ph.D., Purdue University
Postdoctoral, The Wistar Institute
Research Profile
The DNA of eukaryotes is packaged into chromatin by the wrapping of ~146 bp of DNA around a core histone octamer. This packaging serves to compact the DNA into the nucleus, but also presents a barrier to cellular processes, such as transcription, replication and repair, which require access to the DNA. Therefore, controlling access to the chromosomal DNA represents an important regulatory point for these processes. Two major classes of enzymes control access to chromatin. The first class includes enzymes that covalently modify the histones. Examples include acetyltransferases and deacetylases, methyltrasferases, kinases, and ubiquitin ligases. The second major class of enzymes uses the energy of ATP to alter the structure and/or location of the nucleosome. The targeting of these factors to chromatin determines the transcriptional output of a given gene. Control of these transcriptional events can subsequently coordinate cellular events such as apoptosis, proliferation, and differentiation. Disruption of these events is critical to many pathologies including neoplastic transformation and developmental disorders. Indeed, several genes encoding components of chromatin regulatory complexes have been implicated as etiologic agents in many cancers and hereditary malformations.
Projects in our laboratory focus on defining the mechanisms of higher eukaryotic gene regulation through the modification of chromatin structure. Importantly we want to discover how these pathways are linked to development and neoplastic transformation. One example is the connection between the Wnt signaling pathway that controls cell proliferation and fate by regulating transcriptional coactivators that convert a repressed gene to an active gene by reconfiguring chromatin structure. The Wnt/?-catenin signaling pathway performs a vital role in several developmental pathways and has also been shown to be involved in tumorigenesis, particularly colorectal cancers. We have identified a novel protein, CHR1, that can regulate Wnt/?-catenin mediated transcription by using the energy of ATP hydrolysis to alter chromatin structure. Therefore aberrant CHR1 chromatin remodeling activity could be a contributing factor to neoplastic transformation.
Awards
1999 Ching Jer Chern Award, Wistar Inst. Best Scientific Pub.
2001-2002 Christopher Davis Mem. Fellowship for Breast Cancer
2003-present UMMS Biological Scholar
PubMed Search Term : bochar da
Publications
Thompson, B. A., V. Tremblay, G. Lin, and D. A. Bochar. CHD8 is an ATP-dependent Chromatin Remodeling Factor That Regulates {beta}-catenin Target Genes. Mol Cell Biol. 28, 3894-3904 (2008). http://www.ncbi.nlm.nih.gov/pubmed/18378692
Patel, P. D., D. A. Bochar, D. L. Turner, F. Meng, H. M. Mueller, C. G. Pontrello. Regulation of tryptophan hydroxylase-2 gene expression by a bipartite REST/NRSF binding motif. J Biol Chem. 282, 26717-24 (2007). http://www.ncbi.nlm.nih.gov/pubmed/17613521
Lee, M. G., C. Wynder, D. A. Bochar, M. A. Hakimi, N. Cooch, and R. Shiekhattar. Functional interplay between histone demethylase and deacetylase enzymes. Mol Cell Biol. 26, 6395-6402 (2006). http://www.ncbi.nlm.nih.gov/pubmed/16914725
Adams, M. M., B. Wang, Z. Xia, J. C. Morales, X. Lu, L. A. Donehower, D. A. Bochar, S. J. Elledge, and P. B. Carpenter. 53BP1 Oligomerization is Independent of its Methylation by PRMT1. Cell Cycle 4, 1854-1861 (2005). http://www.ncbi.nlm.nih.gov/pubmed/16294047
Hakimi, M.-A., D. A. Bochar, J. A. Schmiesing, Y. Dong, O. G. Barak, D. W. Speicher, K. Yokomori, and R. Shiekhattar. A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418, 994-998 (2002). http://www.ncbi.nlm.nih.gov/pubmed/12198550
Bochar, D. A., Hakimi, M.-A., J. Chonoweth, W. S. Lane, G. Mandel, and R. Shiekhattar. A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc. Natl. Acad. Sci. U S A 99, 7420-7425 (2002). http://www.ncbi.nlm.nih.gov/pubmed/12032298
Bochar, D. A., L. Wang, H. Beniya, A. Kinev, Y. Xue, W. S. Lane, W. Wang, F. Kashanchi, and R. Shiekhattar. BRCA1 is Associated with a Human SWI/SNF-related Complex: Linking Chromatin Remodeling to Breast Cancer. Cell 102, 257-265 (2000). http://www.ncbi.nlm.nih.gov/pubmed/10943845
Bochar, D. A., J. Savard, W. Wang, D. W. Lafleur, P. Moore, J. Cote, and R. Shiekhattar. A family of chromatin remodeling factors related to Williams syndrome transcription factor. Proc. Natl. Acad. Sci. U S A. 97, 1038-1043 (2000). http://www.ncbi.nlm.nih.gov/pubmed/10655480
