With better knowledge about the 3D structural organization of the genome comes the challenge of elucidating which factors determine these structures, what is their functional implications, and how are these structures modulated during cell processes such as cell differentiation or disease progression. Proteins and their complexes play critical roles in orchestrating chromatin interactions and chromosome folding. It is therefore important to link the discovery of endogenous protein complexes with their roles in the formation of specific chromatin interactions. Our goal in this component is to develop a new technology for elucidating the role of protein complexes in chromatin folding. Specifically we combine DNA-DNA proximity mapping with the discovery of the underlying causal protein complexes. We will develop the ?Genome Conformation Capture-Proteome? method (GCCP) for simultaneous detection of chromatin interactions and associated endogenous protein complexes. We will employ a proven pipeline for the isolation of native protein complexes, but extensively optimized for the purpose of reading out the chromatin interactome surrounding the detected specific protein complexes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54DK107981-05
Application #
9783784
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Zhu, Yina; Gong, Ke; Denholtz, Matthew et al. (2017) Comprehensive characterization of neutrophil genome topology. Genes Dev 31:141-153
Dai, Chao; Li, Wenyuan; Tjong, Harianto et al. (2016) Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities. Nat Commun 7:11549
Tjong, Harianto; Li, Wenyuan; Kalhor, Reza et al. (2016) Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proc Natl Acad Sci U S A 113:E1663-72
Shin, Hanjun; Shi, Yi; Dai, Chao et al. (2016) TopDom: an efficient and deterministic method for identifying topological domains in genomes. Nucleic Acids Res 44:e70

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