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Looking at Chromosomes

Authors 

Wu, C. T. - Presenter, Harvard Medical School
Nir, G., Harvard Medical School
Farabella, I., Barcelona Institute of Science and Technology
Estrada, C., Rice University
Ebeling, C., Bruker Nano Inc.
Erceg, J., Harvard Medical School
Abed, J., Harvard Medical School
Goloborodko, A., MIT
McCole, R., Harvard Medical School
Lee, S. H., GTC Technology US LLC
Beliveau, B., Harvard Medical School
Sasaki, H., Harvard Medical School
Nguyen, S., Harvard Medical School
Chattoraj, S., Harvard Medical School
Martins, N., Harvard Medical School
Nguyen, H., Harvard Medical School
Hannan, M., Harvard Medical School
Russell, S., Baylor College of Medicine
Durand, N., Baylor College of Medicine
Rao, S., Rice University
Kishi, J., Harvard University
Soler-Villa, P., Barcelona Institute of Science and Technology
Di Pierro, M., Rice University
Onuchic, J. N., UCSD
Callahan, S., Zero Epsilon
Schreiner, J., Zero Epsilon
Lajoie, B., Harvard Medical School
Fudenberg, G., MIT
Saylor, W., Harvard Medical School
Redon, C., Harvard Medical School
Fonseka, C., Harvard Medical School
Brand, H., Harvard Medical School
Abdennur, N., MIT
Imakaev, M., MIT
Talkowski, M., Broad Institute
Dekker, J., University of Massachusetts Medical School
Mirny, L., MIT
Stuckey, J., Bruker Nano Inc.
Yin, P., Wyss Institute
Lieberman Aiden, E., Rice University
Marti-Renom, M., Universitat Pompeu Fabra
Senaratne, T. N., Harvard Medical School
Joyce, E. F., 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.