The fundamental goals of our work are to understand how eukaryotic cells regulate gene expression. Towards this end, we have focused our efforts on understanding how chromatin and chromatin modification enzymes particpate in gene regulation. These efforts will contribute to a larger effort to understand (and eventually manipulate) epigenetic regulation. At its most basic level, eukaryotic chromosomes contain information on multiple levels. The primary genetic information required for synthesis of most cellular components is encoded in the linear sequence of nucleotide bases incorporated into the DNA polymer. Eukaryotic chromosomes also encode additional information embedded in covalent modification of DNA itself or in the protein components of the chromosome. This information is critical for biological regulation of DNA transactions, including transcription, replication, recombination, and DNA repair. A major challenge for the current generation of biologists is to understand and interpret this 'Epigenetic Code.' Major unanswered questions regarding the epigenetic code include how the information is encoded and what biological systems are responsible for its deposition and for its interpretation. Further, the existence of such a code represents an outstanding opportunity for diagnostic and therapeutic efforts aimed at utilizing information from the Epigenetic Code to improve human health. Of particular interest to the NIEHS mission, it is highly likely that the epigenetic code is strongly impacted by the environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101965-02
Application #
7330696
Study Section
(EDMP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
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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