The position of substructures and DNA sequences within the nucleus is highly organized, and this organization plays a role in regulating chromatin-dependent processes, such as gene expression. X chromosome inactivation is an experimentally amenable example of a phenomenon in which regulated changes in the location of specific DNA sequences is implicated in control of gene expression. In mammalian female cells, one X chromosome is silenced for dosage compensation of X-linked genes between males and females, and this process is essential for female survival. Here, we propose to investigate the molecular basis of the regulated changes in X chromosome nuclear organization that accompany X-inactivation. The insights gained are likely to be more generally applicable, since many of the factors that regulate X-inactivation also regulate gene expression in other contexts.

Public Health Relevance

Early in mammalian development, one of the X chromosomes is silenced in each cell, to equalize X- linked gene dosage between XY males and XX females. X-inactivation is essential for survival of mammalian females, and many of the factors that regulate X-inactivation also regulate gene expression in other contexts. We propose to study the molecular basis of changes in X chromosome organization during X- inactivation. This will provide important information about the role of nuclear organization in X- inactivation and will be relevant to understanding how nuclear organization impacts gene expression for the rest of the genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM100341-03
Application #
8650906
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Carter, Anthony D
Project Start
2012-07-20
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Panning, Barbara; Segal, Eran (2015) Editorial overview: Genome architecture and expression. Curr Opin Genet Dev 31:v-vi
Smith, Elizabeth A; McDermott, Gerry; Do, Myan et al. (2014) Quantitatively imaging chromosomes by correlated cryo-fluorescence and soft x-ray tomographies. Biophys J 107:1988-96
Leung, Karen N; Panning, Barbara (2014) X-inactivation: Xist RNA uses chromosome contacts to coat the X. Curr Biol 24:R80-2
Panning, Barbara (2010) Fine-tuning silencing. Cell Stem Cell 6:3-4