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EECS500 Fall 2017 Department Colloquium

Presenter: 
Fulai Jin, PhD
Title: 
High-resolution Comparative Analysis Reveals a Primitive 3D Genome in Human Embryonic Stem Cells
Affiliation: 
Case Western Reserve University
Location: 
White 411
Time: 
11:30 AM - 12:30 PM
Date: 
November 30, 2017

Identifying chromatin loops from Hi-C data at kilobase resolution remains challenging in 3D genome research. We have improved a fragment-level Hi-C data analysis method, which can resolve both long-range and short-range chromatin loops with no visible biases. In this talk I will present the principle of this new method and how the result may change previous notions about thow genome is organized. We also used this method to compare several billion-scale Hi-C datasets from both embryonic stem cells (ESCs) and differentiated cell types. Most surprisingly, we found that hESCs lack prominent enhancer-mediated chromatin loops. This is in sharp contrast to mESCs and differentiated cells, in which enhancers tether a majority of cell type-specific chromatin loops. Notably, hESCs also lack the pluripotency super-enhancer loops observed in mESCs (near Oct4, Sox2, Nanog and Klf4). The strongest DNA contacts in hESCs are between a few hundred genome loci with highest H3K27me3 occupancy; these repressive chromatin interactions dissolve in differentiated cells along with H3K27me3 redistribution. Our results suggest that hESCs maintain their pluripotency with a primitive enhancer-independent genome architecture, but switch to enhancer-centered architectures during cell fate commitment.

Biography: 

Dr. Fulai Jin has an interdisciplinary background. He got a B.S. degree of biology and a B.E. degree of computer sciences from University of Science and Technology of China (USTC). He then obtained a PhD degree in Molecular and Medical Pharmacology from University of California, Los Angeles (UCLA). In graduate school, Dr. Jin worked in the field of chemical biology performing screens for small molecules or drug target genes using various functional genomic approaches. He developed a smart-pooling method to improve the efficiency of such screening experiments. In the meantime, Dr. Jin also obtained formal training in biostatistics. After graduation, Dr. Jin did his postdoc training with Dr. Bing Ren at Ludwig Institute for Cancer Research and switched to the field of genomics, epigenetics and transcription regulation. During his postdoc, Dr. Jin used a new genomic method called Hi-C and generated the first high-resolution genome-wide map of DNA looping interactions in mammalian cell, which can reveal contacts between any two 5-10kb DNA segments. Such information of 3D genome architecture is critical for our understanding of gene regulation in human diseases. Dr. Jin joined the Genetics Department in 2015 as an assistant professor.