2nd Epigenetics and Bioengineering Conference (EpiBio 2018)

Looking at Chromosomes

Authors

C.-ting Wu - Presenter, Harvard Medical School
Guy Nir, Harvard Medical School
Irene Farabella, Barcelona Institute of Science and Technology
Cynthia Estrada, Rice University
Carl Ebeling, Bruker Nano Inc.
Jelena Erceg, Harvard Medical School
Jumana Abed, Harvard Medical School
Ruth McCole, Harvard Medical School
Soun Ho Lee, GTC Technology US LLC
Brian Beliveau, Harvard Medical School
Hiroshi Sasaki, Harvard Medical School
Son Nguyen, Harvard Medical School
Shyamtanu Chattoraj, Harvard Medical School
Nuno Martins, Harvard Medical School
Huy Nguyen, Harvard Medical School
Mohammed Hannan, Harvard Medical School
Sheikh Russell, Baylor College of Medicine
Neva Durand, Baylor College of Medicine
Suhas Rao, Rice University
Jocelyn Kishi, Harvard University
Paula Soler-Villa, Barcelona Institute of Science and Technology
Michele Di Pierro, Rice University
Steven Callahan, Zero Epsilon
John Schreiner, Zero Epsilon
Bryan Lajoie, Harvard Medical School
Wren Saylor, Harvard Medical School
Claire Redon, Harvard Medical School
Chamith Fonseka, Harvard Medical School
Harrison Brand, Harvard Medical School
Mike Talkowski, Broad Institute
Job Dekker, University of Massachusetts Medical School
Jeff Stuckey, Bruker Nano Inc.
Peng Yin, Wyss Institute
Erez Lieberman Aiden, Rice University
Marc Marti-Renom, Universitat Pompeu Fabra
T. Niroshi Senaratne, Harvard Medical School
Eric F. Joyce, University of Pennsylvania
Our studies of genome organization have led us in a number of directions, including super-resolution imaging of the genome, Hi-C analysis of homolog pairing, and computational analysis of sequence ultraconservation. Regarding imaging, we have developed an approach that enables the tracing of megabases of the human genome at super-resolution using sequence-specific fluorescent in situ hybridization Oligopaint probes and single-molecule localization microscopy (OligoSTORM and OligoDNA-PAINT). Here, we have observed the 3D organization of chromosomal regions contributing to loops, contact domains, and compartments and, using homolog-specific Oligopaint (HOP) probes, have further observed differential packaging of maternal and paternal chromosomal regions. Then, through integrative modeling of genomic regions (IMGR), we have combined our images with Hi-C contact data to generate 3D models of homologous chromosomal regions. Regarding Hi-C analysis of homolog pairing, we have examined both hybrid Drosophila embryos and a newly established hybrid Drosophila cell line to elucidate the structure of homolog pairing and how that pairing accommodates cis interactions in a manner that is correlated with gene expression. Time-permitting, this presentation will also touch on sequence ultraconservation and how its potential underlying mechanism may contribute to the maintenance of genome integrity. This work has benefitted from several collaborations and funding (for the Wu laboratory) from the William Randolph Hearst Foundation to RBM, EMBO (ALTF 186-2014) to JE, and NIH (DP1GM106412, R01HD091797-03, R01GM123289-02) to C-tW.