Hai-Young Wu, Ph.D.
Hai-Young Wu, Ph.D.
Department of Pharmacology
Wayne State University School of Medicine
540 E. Canfield, Detroit MI 48201
Office Phone(313) 577-1584
Office Fax(313) 577-6739
Complex biological events are dependent on the precision of temporal or spatial control of gene expression. The gene expression control is determined by the architectural changes on the chromosome. This is true in both prokaryotic and eukaryotic chromosomes. Toward investigating the effects of chromosome architectural changes on transcription control, our research has focused on the DNA looping and the DNA supercoiling dynamic driven by the transcription processes. We have successfully applied the abundant biophysical information of DNA conformations to the problem of transcription control. We demonstrated that transcription process is a primary driving force that determines chromosome supercoiling dynamic. A supercoiling-sensitive leu-500 promoter was activated by transcription activity of ilvIH promoter located 1.9 kb upstream. We have discovered that the cryptic leuO gene located within the 1.9 kb DNA sequence was responsible for the long-range promoter interaction. This characterizes a promoter relay mechanism in which transcriptional activity from one promoter (i.e. pilvIH) can activate a distant promoter (i.e. pleu-500) via activation of an intermediate promoter (i.e. pleuO). The gene product of leuO, LeuO, plays a trans-acting role in this novel transcription coordination. Data suggested that transcription elements involved in coordinated gene expression are responsive to DNA supercoiling driven by the adjacent transcription activities. The striking DNA supercoiling responsiveness has led to the finding of a novel gene silencing and anti-silencing mechanism whereby expression of multiple genes in the gene cluster is controlled in a sequential manner. Indeed, a heterochromatic nucleoprotein filament was found to be responsible for the bacterial gene silencing. A bacterial boundary element-like activity is responsible for the anti-silencing mechanism. The bacterial protein, LeuO, evidently exerted its boundary element-like activity by forming various DNA loops important in the transcriptional regulation. Our most recent work demonstrated that LeuO is a chromosome architectural protein that is capable of converting a gene repression complex into a gene activation complex by modulating the structural of a 47-bp DNA element. The unraveled mechanism is paradigmatic for the expression regulation of eukaryotic genes.
Ph.D. in Biochemistry, City University of New York, Graduate Center. 1985
Postdoctoral Fellowship, Department of Biochemistry, The Johns Hopkins University, School of Medicine. 1986-1991
Areas of Expertise
Biochemistry and Molecular Biology
- Chen, C.-C., Ghole, M., Majumder, A., Wang, Z. Chandana, S., and Wu, H.-Y. (2003) “ LeuO-mediated transcriptional derepression” J. Biol. Chem. 278, 38094-38103
- Chen, C.-C., Chou , M.-Y., Huang, C.-H., Majumder, A., and Wu, H.-Y. (2005)“A cis-spreading nucleoprotein filament is responsible for the gene silencing activity found in the promoter relay mechanism” J. Biol. Chem. 280, 5101-5112
- Chen, C.-C., and Wu, H.-Y. (2005) “LeuO protein delimits the transcriptionally active and repressive domains on the bacterial chromosome.” J. Biol. Chem. 280, 15111-15121
- Chen, C.-C., and Wu, H.-Y. (2003)“Transcription-driven DNA supercoiling and gene expression control” in the encyclopedia of “ DNA supercoiling and gene expression” in Frontiers in Bioscience, 8, 430-439.
- Wu, H.-Y. & Fang, M. (2003) “ DNA supercoiling & transcription control: A model from the study of suppression of the leu-500 mutation in Salmonlla typhimurium topA- mutants.” Progress in Nucleic Acid Research and Molecular Biology, vol. 73, pp 41- 66. Edited by Kivie Moldave. Academic Press.
- Chen, C.-C., and Wu, H.-Y. (2006) Genome organization: The effects of transcription-driven DNA supercoiling on gene expression regulation, Chapter 28, pp. 458-469 In: Gene Expression and Regulation, (ed. J. Ma), a Current Scientific Frontiers Book, Higher Education Press & Springer. http://www.amazon.com/o/ASIN/0387332081/ref=pe_snp_081