Deciphering the transcriptional regulatory code 

Topic: Deciphering the transcriptional regulatory code 

Speaker: Yong Cheng , Ph.D.

             Postdoc,Department of Genetics, Stanford University, Stanford

Host: Professor GAO Shaorong

Time: 10:00AM-11:30AM, 20th MAY, 2015

Venue: Room 1102, Medical Buidling

Intro:

Cir-regulatory modules are the key components of gene regulatory networks and essential to understand the human genome that encodes the blueprint of life. To broaden our understanding gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human–mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences. Our results illuminate the wide range of evolutionary forces acting on regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.