Biological and Biomedical Science
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C.-ting Wu (Ting)

Department of Genetics
Harvard Medical School
New Research Building, Room 264
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 432-4431 (office), -4432 (lab)
Fax: (617) 432-7663
Email: twu@genetics.med.harvard.edu
Web Page: The Wu (Ting) Lab Page
1 postdoctoral fellow, 3 graduate students

Chao-Ting Wu

The presence of homology can have profound consequences for gene activity and chromosome behavior. Our interest in this area has led us to a number of topics (below). We are also the home for pgEd, which introduces and promotes conversations about personal genetics and its implications for society and medicine (http://pgEd.org).

Transvection: Transvection is best understood in Drosophila, where homologous chromosomes are paired in somatic cells. Here, transvection can occur when enhancers act in trans on a promoter lying on a separate chromosome or when pairing-mediated changes in gene conformation alter gene expression. Using genetic, molecular biological, and cytological approaches, we are working to elucidate this peculiar form of gene regulation.

Homologue pairing: Homolog pairing is critical for many homology effects and also for gene replacement strategies. We have developed a system for studying pairing in cell culture and are using it in a candidate gene approach as well as a whole-genome RNAi-driven screen to look for genes that mediate and/or control pairing. Thus far, we have identified topoisomerase II. Ultimately, we will extend our efforts to mammalian systems.

Chromosome segregation: We are determining whether sister chromatid segregation of one chromosome is random with respect to that of its homolog after mitotic recombination. This analysis extends a handful of studies in Drosophila and mice showing that such segregation can be nonrandom in some tissues. Our goal is to determine whether nonrandom patterns are tissue specific as well as identify the genes that control the nonrandom patterns.

 PcG genes: We have found that some genes of the PcG, which encode chromatin proteins, are important for pairing-associated phe­no­types. Currently, our work focuses on Psc and Su(z)2, two adjacent PcG genes. Using genetic and molecular biological tools, we have defined functional do­mains within the Psc protein and are ex­panding our study to the Su(z)2 protein.

Ultraconserved elements: One striking outcome of genome analyses is the identification of ultraconserved elements (UCEs), which are essentially invariant among distantly related species. We have found that UCEs are depleted among human copy number variants. This finding suggests a model in which UCEs act as genomic copy counters, perhaps via pairing and sequence comparison of the maternal and paternal copies of each UCE.

X-inactivation: Our interest in homology effects has led us to a theoretical reconsideration of current models for mammalian X-inactivation, which is widely believed to involve a random choice between the maternal and paternal X chromosomes.  In particular, we have proposed two alternative models.  One suggests that choice is not random, while the other is consistent with random choice, but not one between two X chromosomes.

References:

  • Bateman, J. R., A. M. Lee, and C.-t. Wu. 2006. Site-specific transformation of Drosophila via phiC31 integrase-mediated cassette exchange. Genetics 173: 769-77.
  • Derti, A., F. P. Roth, G. M. Church, and C.-t. Wu. 2006. Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Nat. Gen. 38: 1216-20.
  • Lee, A., C.-t. Wu. 2006. Enhancer-promoter communication at the yellow gene of Drosophila melanogaster: Diverse promoters participate in and regulate trans interactions. Genetics 174: 1867-80.
  • Williams B.R., Bateman J.R., Novikov N.D., Wu C.-t. 2007. Disruption of topoisomerase II perturbs pairing in Drosophila cell culture. Genetics 177: 31-46.