C.-ting (Ting) Wu

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) 432-6513
Email: twu@genetics.med.harvard.edu
Web Page: The Wu (Ting) Lab Page
1 postdoctoral fellow, 3 graduate students

Homology can have profound consequences for gene activity and chromosome behavior, and our interest in this area has led us to a number of topics. We are also the home for pgEd, which promotes conversations about personal genetics and its implications for society (http://pgEd.org). We work with Drosophila, mammalian, and nematode systems using genetics, molecular biology, biochemistry, cytology, chromosome painting, and bioinformatics.

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 in a whole-genome RNAi-driven screen to look for genes that mediate and/or control pairing. Thus far, we have identified topoisomerase II. We are now embarking on analyses in human systems.

Transvection: Transvection encompasses surprising 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. Using genetic, molecular biological, and cytological tools, we are elucidating this peculiar form of gene regulation, exploring the potential of pairing to exert its effect by altering gene conformation.

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. We have identified functional domains within both the Psc and Su(z)2 proteins and are now conducting genetic, molecular biological, and biochemical analyses to more finely dissect these domains.

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:

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.
Chiang CWK, Derti A, Schwartz D, Chou MF, Hirschhorn JN, and Wu C-t. 2008. Ultraconserved elements: Analyses of dosage sensitivity, motifs, and boundaries. Genetics 180: 2277-93.
Griffin R, Sustar A, Bonvin M, Binari R, et al. 2009. The twin spot generator technique for differential Drosophila lineage analysis. Nature Methods (in press).
Emmons RB, Genetti H, Filandrinos S, Lokere J, and Wu C-t. 2009. Molecular genetic analysis of Su(z)2 identifies key functional domains. Genetics (in press).

BBS webpage updated 12/02/2009