Speaker: Yijun Ruan, Genome Institute of Singapore
Topic: 3D Chromosomal Architectures and Transcriptional Regulation
Venue: Medical School seminar room B323
Time & Date: Monday, August 6, 2013 – 2:00 – 3:30pm

Abstract: Genomes are known to be organized into 3-dimensional (3D) conformation in vivo through interactions with protein factors for nuclear process such as transcription, and DNA elements separated by long genomic distances are known to functionally interact. However, the details of this view are largely unknown. To study long-range chromatin interactions mediated by protein factors, we developed Chromatin Interaction Analysis using Paired-End-Tag sequencing (ChIA-PET), and applied ChIA-PET analysis to detect all chromatin interactions involved in gene transcription regulation that are associated with RNA polymerase II (RNAPII). In these analyses, we identified widespread promoter-centered interaction including intra-, extra-, and inter-genic chromatin interactions, of which the vast majority was intra-chromosomal (98% of all interactions). Many interactions further congregate into complex interaction structures. While some genes were involved in “single-gene” interactions (enhancer-promoter interactions), surprisingly, large number of genes were involved in “multi-gene” interaction complexes including promoter-promoter and enhancer-promoter interactions, some of which could span up to several megabases. The extensive promoter-promoter interactions are in principle akin to the bacterial operon as a mechanism for coordinated transcriptional regulation of related proximal genes, suggesting the possibility of a chromatin-based operon mechanism (chro-operon or chroperon) for spatiotemporal regulation of gene transcription in eukaryotic nuclei. We demonstrated that genes in chroperons could transcribe cooperatively, and discovered that promoters could influence each other, implying higher-order combinatorial complexity of transcriptional controls. Overall, our studies provided new dimension of combinatorial controls of gene transcription within the context of chromatin looping architecture in eukaryotic
genomes, and paved the way towards presenting the 3D topographic maps of the human genomes.