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
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 ER? alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, and HDAC2) in the mouse seminal vesicle. Environ Health Perspect 122:262-8
Markunas, Christina A; Xu, Zongli; Harlid, Sophia et al. (2014) Identification of DNA Methylation Changes in Newborns Related to Maternal Smoking during Pregnancy. Environ Health Perspect :
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
Li, Ruifang; Grimm, Sara A; Chrysovergis, Kaliopi et al. (2014) Obesity, rather than diet, drives epigenomic alterations in colonic epithelium resembling cancer progression. Cell Metab 19:702-11
Allen, Hillary F; Daze, Kevin D; Shimbo, Takashi et al. (2014) Inhibition of histone binding by supramolecular hosts. Biochem J 459:505-12
Adomas, Aleksandra B; Grimm, Sara A; Malone, Christine et al. (2014) Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover. BMC Cancer 14:278
Li, Ruifang; Mav, Deepak; Grimm, Sara A et al. (2014) Fine-tuning of epigenetic regulation with respect to promoter CpG content in a cell type-specific manner. Epigenetics 9:747-59
Wade, Paul A (2014) Are genomic translocations predictable? (Retrospective on DOI 10.1002/bies.201100122). Bioessays 36:633
Godfrey, Ashley C; Xu, Zongli; Weinberg, Clarice R et al. (2013) Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort. Breast Cancer Res 15:R42

Showing the most recent 10 out of 13 publications