Two Case Studies of Transcriptional Regulation
Event Type: Seminar
Date: February 19, 2008
Time:
01:00PM
- 02:30PM
Venue:
CC-2-2540
Abstract:
During this talk, I will present two studies recently performed in our
lab, one broad and one specific.
In the first case study, we discribe the identification of regulatory
elements from different cell types for understanding the mechanisms
controlling cell type-specific and housekeeping gene expression. Mapping
DNaseI hypersensitive (HS) sites is an accurate method for identifying the
location of functional regulatory elements. We used a high throughput
method called DNase-chip to identify 3,904 DNaseI HS sites from six cell
types across 1% of the human genome. A significant number (22%) of DNaseI
HS sites from each cell type are ubiquitously present among all cell types
studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites
correspond to either promoters or insulator elements. We also identified a
large number of DNaseI HS sites that are cell type specific (only present
in one cell type); these regions are enriched for enhancer elements and
correlate with cell type-specific gene expression as well as cell
type-specific histone modifications.
In the second case study, we compiled and analyzed a set of 723
high-quality human core promoter sequences for overrepresented motifs.
Beside previously known motifs (including YY1), one potentially new motif
(motif8) were found. Interestingly, YY1 and motif8 mostly reside
immediately downstream from the TSS. In particular, the YY1 motif occurs
primarily in genes with 5'-UTRs shorter than 40 base pairs (bp) and its
locations coincide with the translation start site. We then performed
detailed analysis on YY1 chromatin immunoprecipitation data with a
whole-genome human promoter microarray (ChIP-chip) and revealed that the
thus identified promoters in HeLa cells were highly enriched with the YY1
motif. Moreover, the motif overlapped with the translation start sites on
the plus strand of a group of genes, many with short 5'-UTRs, and with the
transcription start sites on the minus strand of another distinct group of
genes; together, the two groups of genes accounted for the majority of the
YY1-bound promoters in the ChIP-chip data.
Speaker:
Zhiping Weng
Speaker Bio:
Zhiping Weng graduated from the University of Science and Technology of
China in 1992 with B.S. in Electrical Engineering. In 1993, she entered
the graduate program in Biomedical Engineering at Boston University, and
received her Ph.D. in 1997. The focus of her thesis research was in
computational biology, specifically on calculating binding free energies
of protein-protein interactions. In January 1997 Dr. Weng was appointed
Instructor of Biomedical Engineering at Boston University. In that
capacity she taught and conducted research, and had primary
responsibility for the development of the Bioinformatics program and the
core curriculum in Bioinformatics. In January 1999 the Biomedical
Engineering Department at Boston University decided to grow in the area
of Bioinformatics. After a national search, the department appointed
Dr. Weng a tenure-track assistant professor. In September 2003, Dr. Weng
was promoted to Associate Professor with tenure. Until December 2007,
Dr. Weng’s research had been focused on developing computational methods
to obtain a predictive understanding of transcriptional regulation and
protein-protein interaction. She had published 90 articles, including 75
peer-reviewed journal articles. On 1 January 2008, Dr. Weng moved to
University of Massachusetts Medical School to build and direct a new
Program in Bioinformatics and Integrative Biology. She is a full
professor, with tenure in Department of Biochemistry and Molecular
Pharmacology. She continues research on computational analysis of
transcriptional regulation. She has started to study epigenomics and
nucleosome positioning, which play important roles in transcriptional
regulation. In addition, she is investigating the function and
regulation of small RNAs in metazoan. For more information, please visit
Dr. Weng's lab Website (
http://zlab.bu.edu).
