Eukaryotic Transcriptional Regulation

Wade, Paul A.

Abstract

Research accomplishments 1. We have defined an environmental signaling axis that regulates the stability of a regulatory subunit of the human Mi-2/NuRD complex. This signaling pathway may play a role in determination of phenotypic properties of malignant cells. 2. We have defined new epigenetic regulation at a key oncogene critical to lymphomagenesis. 3. We have identified a role for the Mi-2/NuRD complex in the process of chromosome duplication and have made progress in understanding how this complex plays a role in this process. 4. We have established in our laboratory a new system for genomic scale analysis of epigenetic parameters of gene expression. 5. We have utilized genomic scale analysis of DNA methylation to identify epigenetic alterations in B lymphocytes that occur druring immune activation. We have tied these epigenetic alterations to biological pathways integral to the adaptive immune response.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAES101965-06
• Application #: 8149095
• Support Year: 6
• Fiscal Year: 2010
• Total Cost: $2,189,818

Institution

• Name: National Institute of Environmental Health Sciences

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