Faculty

Christine M. Disteche, Ph.D.

Professor of Pathology,
Adjunct Professor of Medicine

University of Washington
C-526 Health Sciences Building
Pathology, Box 357470
Phone: 206-543-0716
FAX: 206-543-3644
E-mail: cdistech@u.washington.edu

Research Profile (Community of Science)

The focus of the Disteche lab is the study of the regulation of the mammalian sex chromosomes. Divergence between the sex chromosome has led to special types of regulation. The best known form of regulation of the X chromosome is X inactivation, which silences one X chromosome in females. We recently discovered that the X chromosome is subject to another form of dosage compensation, which consists in a doubling of transcriptional output from the single active X chromosome to equalize expression with the autosomes present in two copies. This novel form of dosage compensation maintains a balanced expression of the genome. We also found higher expression of X-linked genes in brain versus other tissues. The special role of the X chromosome in brain function is relevant to the study of X-linked mental retardation. Our current goals are to characterize the molecular mechanisms of X chromosome up-regulation in mammals in terms of chromatin structure and timing during development. In addition, we are studying the role and molecular structure of genes that escape X inactivation (i.e. expressed from both X chromosomes in females). We have found that these genes have different expression levels between males and females, which may explain some of the phenotypic differences between the sexes. We are interested in investigating the role of these genes in sex chromosome disorders.

Investigator: Christine Disteche is a Professor in the Department of Pathology and Adjunct Professor in Medicine

Publications:

Graves JA, Disteche CM (2007) Does gene dosage really matter?, Journal of biology, 6(1)1

Nguyen DK, Disteche CM (Dec 2006) High expression of the mammalian X chromosome in brain., Brain research, 1126(1)46-9

Xu J, Disteche CM (Dec 2006) Sex differences in brain expression of X- and Y-linked genes., Brain research, 1126(1)50-5

Heard E, Disteche CM (Jul 2006) Dosage compensation in mammals: fine-tuning the expression of the X chromosome., Genes & development, 20(14)1848-67

Nguyen DK and Disteche CM (2006) Dosage compensation of the active X chromosome in mammals., Nature Genetics, 3847-53

Cheng MK, Disteche CM (2006) A balancing act between the X chromosome and the autosomes., Journal of biology, 5 (1), 2

Nguyen DK, Disteche CM (Jan 2006) Dosage compensation of the active X chromosome in mammals., Nature genetics, 38 (1), 47-53

Okamoto I, Arnaud D, Le Baccon P, Otte AP, Disteche CM, Avner P, Heard E (Nov 2005) Evidence for de novo imprinted X-chromosome inactivation independent of meiotic inactivation in mice., Nature, 438 (7066), 369-73

Filippova GN, Cheng MK, Moore JM, Truong JP, Hu YJ, Nguyen DK, Tsuchiya KD, Disteche CM (Jan 2005) Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development., Developmental cell, 8 (1), 31-42

Tsuchiya KD, Greally JM, Yi Y, Noel KP, Truong JP, Disteche CM (Jul 2004) Comparative sequence and x-inactivation analyses of a domain of escape in human xp11.2 and the conserved segment in mouse., Genome research, 14 (7), 1275-84

Disteche CM, Filippova GN, Tsuchiya KD (2002) Escape from X inactivation., Cytogenetic and genome research, 99 (1-4), 36-43

Leppig KA, Disteche CM, Ring X and Other Structural X chromosome abnormalities: X inactivation and Phenotype, Seminars in Reproductive Medicine, 19, 147-158, 2001

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