Research accomplishments 1. We have made significant progress in dissecting the relationship between obesity and epigenetic alterations in the colon that my predispose to cancer. We find that a microbiome specific to obese animals metabolizes an obesogenic diet to produce metabolites that impact the colon epigenome. 2. 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. 3. 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. 4. We have made progress in understanding the role of the de novo DNA methyltransferase DNMT3a in the maintenance of DNA methylation in B lymphocytes.

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Budget End
Support Year
14
Fiscal Year
2018
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Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
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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

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