Research Interests of Dr. Shu Xiang Zhang

Serum response factor (SRF) is an obligatory transcription factor that is required for the formation of vertebrate mesoderm leading to the origin of the cardiovascular system. Currently, there are a limited number of direct SRF gene targets, which are regulated during the formation of early cardiovascular mesoderm.

I developed a chromatin immunoprecipitation assay to explore regulatory networks in the developing cardiovascular mesoderm. The great advantage of combining global transcription factor binding analysis with expression profiling is that the direct targets of transcription factors can be distinguished from indirect downstream effects. Chromatin immunoprecipitation (ChIP) is a powerful tool for elucidating in vivo DNA-protein interactions. I developed a systematic non-biased search for downstream sequence genes that may be directed through SRF to capture genetic targets. A generic protocol was devised to purify the DNA fragments bound to SRF in vivo from the whole genome by Protein A-TEV-Tagged Chromatin Immunoprecipitation. I used PATChIP technology to purify the DNA fragments bound in vivo to serum response factors (SRF) and identified more than 200 SRF targets. My PATChIP system is being harnessed to explore regulatory network of other transfactors in the developing cardiovascular system.

Representative Publications

Zhang, S.X., Garcia-Gras, E., Wycuff, D.R., Marriot, S.J., Kadeer, N., Yu, W., Olson, E.N., Garry, D.J., Parmacek, M.S., Schwartz, R.J. (2005) Identification of direct serum-response factor gene targets during Me2SO-induced P19 cardiac cell differentiation. J Biol Chem. 2005 280:19115-19126

Barron, M.R., Belaguli, N.S., Zhang, S.X., Trinh, M., Iye,r D., Merlo, X., Lough, J.W., Parmacek, M.S., Bruneau, B.G., Schwartz, R.J. (2005) Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes. J Biol Chem. 280:11816-11828.

Niu, Z., Yu, W., Zhang, S.X., Barron, M., Belagul,i N.S., Schneider, M.D., Parmacek, M., Nordheim, A., Schwartz, R.J. (2005) Conditional mutagenesis of the murine serum response factor gene blocks cardiogenesis and the transcription of downstream gene targets. J Biol Chem. [E-pub ahead of print]