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.

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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
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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

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