Abstract

Chromatinorganizationandepigenomicmodificationssuchascytosinemethylationplayinstrumentalroles ingeneregulationduringhumandevelopmentandinhealthyanddiseasestates.Althoughthegenomeis nearlyidenticalineachcellinthehumanbody,chromatinconformationandcytosineDNAmethylationare highlydynamicacrosscelltypesandduringdevelopment.Previousstudiesshowedthatchromatinlooping canberegulatedbycytosinemethylation.However,ourcurrentstateofknowledgeoftheinteractions betweenchromatinorganizationandDNAmethylationisbuiltonanalyzingculturedcellsandbulktissues. Theinteractionbetweencell-typespecificchromatinloopingandmethylationinheterogeneoustissues remainlargelyunexplored.Thisprojectwilldevelopsingle-cellmulti-omicmethodstojointlyanalyze chromatinconformationandcytosinemethylationfromthesamecell.Themethodswillleadtohighquality cell-typespecificchromatinconformationmapsofhumantissue,andtheanalysisoftherelationship betweenchromatinconformationandcytosinemethylation.Ifsuccessful,theproposedmethodswillgreatly facilitatethestudyofgeneregulationincomplexhumantissuesandinheterogeneousdiseasessuchas cancer.

Public Health Relevance

Thegoaloftheprojectistodevelopmethodstostudytheinteractionbetweenatypeofchemical modificationtoDNA-cytosinemethylation-andthethree-dimensionalorganizationofthehumangenome. Cytosinemethylationandgenomeorganizationaretwoimportantmechanismstocontrolgeneexpression inhealthyanddiseasedtissues.Thesemethodswillallowthegenerationofmulti-dimensionalDNA methylationandgenomeorganizationmapsfromsinglehumancells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG010634-02
Application #
10009414
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chadwick, Lisa
Project Start
2019-09-06
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037