Research accomplishments ? ? 1. We have further extended our knowledge of the estrogen receptor MTA3 Snail genetic pathway in the context of breast cancer. We have determined that exogenous expression of Snail in ER positive cell lines leads to loss of expression of ER itself. Chromatin immunoprecipitation experiments indicate that Snail directly associates with regulatory DNA at the ESR1 locus leading to repression, but not stable silencing, of ER expression. ? 2. We have determined that MTA3 serves as a useful marker in diagnosis of lymphomas. The protein is expressed at high levels in lymphomas of germinal center or post-germinal center origin. High level expression of MTA3 strongly predicts a germinal center pattern of gene expression.? 3. We have identified a role for the Mi-2/NuRD complex in the process of chromosome duplication.? 4. We have identified an unexpected role for DNA methylation in expression of an oncogene critical to lymphomagenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101965-04
Application #
7734547
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2008
Total Cost
$1,658,625
Indirect Cost
City
State
Country
United States
Zip Code
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
Duncan, Christopher G; Grimm, Sara A; Morgan, Daniel L et al. (2018) Dosage compensation and DNA methylation landscape of the X chromosome in mouse liver. Sci Rep 8:10138
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
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
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
Zhang, Song; Takaku, Motoki; Zou, Liyun et al. (2017) Reversing SKI-SMAD4-mediated suppression is essential for TH17 cell differentiation. Nature 551:105-109
Shimbo, Takashi; Takaku, Motoki; Wade, Paul A (2016) High-quality ChIP-seq analysis of MBD3 in human breast cancer cells. Genom Data 7:173-4
Takaku, Motoki; Grimm, Sara A; Shimbo, Takashi et al. (2016) GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler. Genome Biol 17:36
Takaku, Motoki; Grimm, Sara A; Wade, Paul A (2015) GATA3 in Breast Cancer: Tumor Suppressor or Oncogene? Gene Expr 16:163-8

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