Abstract

Research accomplishments 1. We have identified an interaction between obesity and the landscape of regulatory DNA in the mouse colon. Our experiments define a pattern of enhancer utilization in the colon that resembles cancer progression and is initiated by obesity. 2. We are studying the ability of the transcription factor GATA3 to pioneer new enhancer sites in genomic chromatin. Our experiments indicate that GATA3 utilizes a two-step mechanism to create new enhancers. 3. We have made significant progress in understanding the relationship between cancer-specific mutations found in the transcription factor GATA3 and epigenetic regulation of gene expression that may contribute to breast cancer outcomes. 4. We have made significant progress in understanding the genomic distribution of NuRD complex in breast cancer cells and how this enzyme contributes to the biological program of breast cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES101965-12
Application #
9352133
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Takaku, Motoki; Grimm, Sara A; Roberts, John D et al. (2018) GATA3 zinc finger 2 mutations reprogram the breast cancer transcriptional network. Nat Commun 9:1059
Duncan, Christopher G; Kondilis-Mangum, Hrisavgi D; Grimm, Sara A et al. (2018) Base-Resolution Analysis of DNA Methylation Patterns Downstream of Dnmt3a in Mouse Naïve B Cells. G3 (Bethesda) 8:805-813
Li, Ruifang; Grimm, Sara A; Mav, Deepak et al. (2018) Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer. Cell Rep 22:624-637
Takizawa, Yoshimasa; Tanaka, Hiroki; Machida, Shinichi et al. (2018) Cryo-EM structure of the nucleosome containing the ALB1 enhancer DNA sequence. Open Biol 8:
Wilczewski, Caralynn M; Hepperla, Austin J; Shimbo, Takashi et al. (2018) CHD4 and the NuRD complex directly control cardiac sarcomere formation. Proc Natl Acad Sci U S A 115:6727-6732
Li, Yin; Hamilton, Katherine J; Wang, Tianyuan et al. (2018) DNA methylation and transcriptome aberrations mediated by ER? in mouse seminal vesicles following developmental DES exposure. Proc Natl Acad Sci U S A 115:E4189-E4198
Qin, Yufeng; Roberts, John D; Grimm, Sara A et al. (2018) An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression. Genome Biol 19:7
Thomas, S Y; Whitehead, G S; Takaku, M et al. (2018) MyD88-dependent dendritic and epithelial cell crosstalk orchestrates immune responses to allergens. Mucosal Immunol 11:796-810
Qin, Yufeng; Wade, Paul A (2018) Crosstalk between the microbiome and epigenome: messages from bugs. J Biochem 163:105-112
Shimbo, Takashi; Dunnick, June K; Brix, Amy et al. (2017) DNA Methylation Changes in Tbx3 in a Mouse Model Exposed to Polybrominated Diphenyl Ethers. Int J Toxicol 36:229-238

Showing the most recent 10 out of 51 publications