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 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. Our data suggest the existence of a previously undescribed checkpoint monitoring chromatin quality during the process of chromosomal duplication. 3. We have begun exploration of chromatin modifications and their relationship to gene expression in primary cells from mice. 4. 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 transcription factor and DNA methyltransferase function. 5. 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. 6. We have begun analysis of genome modification in an exposure model of cancer.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2013
Total Cost
$1,931,622
Indirect Cost
City
State
Country
Zip Code
Lu, Rui; Wang, Ping; Parton, Trevor et al. (2016) Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development. Cancer Cell 30:92-107
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
Markunas, Christina A; Wilcox, Allen J; Xu, Zongli et al. (2016) Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PLoS One 11:e0156361
Takaku, Motoki; Grimm, Sara A; Wade, Paul A (2015) GATA3 in Breast Cancer: Tumor Suppressor or Oncogene? Gene Expr 16:163-8
Cekanova, Maria; Fernando, Romaine I; Siriwardhana, Nalin et al. (2015) BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion. Exp Cell Res 331:1-10
Wang, Li; Du, Ying; Ward, James M et al. (2014) INO80 facilitates pluripotency gene activation in embryonic stem cell self-renewal, reprogramming, and blastocyst development. Cell Stem Cell 14:575-91
Allen, Hillary F; Daze, Kevin D; Shimbo, Takashi et al. (2014) Inhibition of histone binding by supramolecular hosts. Biochem J 459:505-12
Menafra, Roberta; Brinkman, Arie B; Matarese, Filomena et al. (2014) Genome-wide binding of MBD2 reveals strong preference for highly methylated loci. PLoS One 9:e99603
Li, Yin; Hamilton, Katherine J; Lai, Anne Y et al. (2014) Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262-8

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