BBS Faculty Member - Chao-ting Wu

Chao-ting Wu

Department of Genetics

Harvard Medical School
New Research Building, Room 264
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-4431
Fax: 617-432-7663
Email: twu@genetics.med.harvard.edu
Lab Members: 3 postdoctoral fellows, 5 graduate students
Visit my lab page here.



Chromosome positioning can dramatically affect genome activity, stability, and inheritance. Focusing on mammals, Drosophila, and nematodes, and using molecular genetics, biochemistry, and bioinformatics, we are studying chromosome positioning as it pertains to homolog pairing, Polycomb group (PcG) genes, ultraconserved elements (UCEs), transvection, and loss-of-heterozygosity (LOH) as well as developing technologies to better visualize chromosomes. We are also the home for pgEd, which accelerates education on personal genetics (http://pgEd.org).

Homologue pairing: Using a method we developed for high-throughput FISH, we are conducting whole-genome screens to look for genes that control the pairing of homologous chromosomes in nonmeiotic (somatic) cells in Drosophila and mammals. These studies support a model in which the state of pairing reflects both pairing and anti-pairing activities and have brought us face-to-face with the cell cycle, sister chromatid cohesion, and ploidy.

Oligopaints: We have developed a technology, called Oligopaints, for visualizing chromosomes with fluorescent probes. It should enable high-throughput FISH studies targeting single-copy regions such that researchers can trace the path of chromosomes through the nucleus while exploring the relationship between chromatin structure and gene expression. We are also exploring the applicability of Oligopaints to super-resolution microscopy.

Polycomb group (PcG) genes: We have found that some genes of the PcG, which encode chromatin proteins, are important for pairing-associated phenotypes. Our work focuses on two such genes, Psc and Su(z)2, where we have identified several functional domains and obtained evidence for intramolecular regulation. We are now exploring how Psc and Su(z)2 control gene expression both in vivo and in cell culture.

Ultraconserved elements (UCEs): The perfect conservation of UCEs between distantly related species cannot be explained by known protein-coding or regulatory functions. Instead, UCEs may act to maintain genome integrity via pairing and sequence comparison. We are testing this model using population genetics and bioinformatics to reveal the relationship between UCEs and copy number variants (CNVs), selection pressure, and disease.

Transvection: Transvection encompasses mechanisms of gene regulation that permit a gene to influence a homologous gene when the two are paired, in some cases causing enhancers to act in trans on a promoter lying on a separate chromosome. We are elucidating this form of gene regulation, exploring the potential of pairing to exert its effect by altering gene conformation.

Loss-of-heterozygosity (LOH): There are a number of chromosomal and gene regulatory mechanisms that can cause a diploid cell to be functionally haploid. These include mechanisms such as LOH through mitotic recombination, X-inactivation, random mononallelism, and parental imprinting. We are exploring these phenomena in mammalian and Drosophila cells.



Last Update: 1/7/2014



Publications

Derti A, Roth FP, Church GM, and Wu C-t. Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Nat Genet. 2006 38:1216-20 PMID: 16998490.

Bateman JR, Wu C-t. A genome-wide survey argues that every zygotic gene product is dispensable for the initiation of somatic homolog pairing in Drosophila. Genetics 2008; 180:1329-42. PMID: 18791221, PMCID: PMC2581938.

Chiang CWK, Derti A, Schwartz D, Chou MF, Hirschhorn JN, Wu C-t. Ultraconserved elements: Analyses of dosage sensitivity, motifs, and boundaries. Genetics. 2008 180:2277-93. PMID: 18957701, PMCID: PMC2600958.

Ou SA, Chang E, Lee S, So K, Wu C-t, Morris JR. Effects of chromosomal rearrangements on transvection at the yellow gene of Drosophila melanogaster. Genetics 2009; 183:483-96 PMID: 19667134, PMCID: PMC2766311.

Joyce EF, Williams BR, Xie T, Wu C-t. Indentification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen. PLoS Genetics 2012; 8: e1002667. PMCID: PMC3349724.

Hohl AM, Thompson M, Soshnev AA, Wu J, Morris J, Hsieh T-S, Wu C-t, Geyer PK. Restoration of Topoisomerase 2 function by complementation of defective monomers in Drosophila. Genetics 2012; 192: 843-56. PMID: 22923380. PMCID: PMC3522162.

Beliveau BJ*, Joyce ER*, Apostolopoulos N, Yilmaz F, Fonseka CY, McCole RB, Chang Y, Li JB, Senaratne TN, Williams BR, Rouillard J-M, Wu C-t. A versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes. Proc. Nat. Acad. Sci. USA 2012; 109:213101-6. PMID: 23236188; PMCID: PMC3535588.

Joyce ER, Apostolopoulos N, Beliveau BJ, Wu C-t. Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development. PLoS Genetics 2013 9:e1004013.



© 2013 by the President and Fellows of Harvard College