Abstract

During FY2000 we built upon key observations that we made concerning the mechanisms by which steroid receptors activate transcription within breast cancer cells. We demonstrated that proteins involved in the manipulation of chromatin structure, so called chromatin remodeling machines, represent the key components in the cascade of events that results in the activation of the genetic program in human breast cancer cells. We have analyzed the activity of the glucocorticoid receptor within breast and Osteosacoma cancer cells that differ in the expression of components of the chromatin remodeling machines. These cells display an altered response to a variety of clinically important hormone antagonist and will be useful in evaluating various anti-hormone strategies in breast cancer. In addition they are a unique resource to evaluate and characterize the impact of a number of environmental agents in human cells. To this end we have continued to develop methodologies that allow us to look a protein-DNA interactions within living cells,in vivo footprinting, as well as changes at the control regions of specific genes within living cell, chromatin immunoprecipitation (CHIP) assays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES071006-02
Application #
6432405
Study Section
(LRDT)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Singh, Ajeet Pratap; Foley, Julie; Tandon, Arpit et al. (2017) A role for BRG1 in the regulation of genes required for development of the lymphatic system. Oncotarget 8:54925-54938
Singh, Ajeet P; Foley, Julie F; Rubino, Mark et al. (2016) Brg1 Enables Rapid Growth of the Early Embryo by Suppressing Genes That Regulate Apoptosis and Cell Growth Arrest. Mol Cell Biol 36:1990-2010
Lavender, Christopher A; Cannady, Kimberly R; Hoffman, Jackson A et al. (2016) Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters. PLoS Genet 12:e1006224
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
Yang, Jun; Bennett, Brian D; Luo, Shujun et al. (2015) LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells. Mol Cell Biol 35:3225-43
Wade, Staton L; Langer, Lee F; Ward, James M et al. (2015) MiRNA-Mediated Regulation of the SWI/SNF Chromatin Remodeling Complex Controls Pluripotency and Endodermal Differentiation in Human ESCs. Stem Cells 33:2925-35
Zhang, Xiaoli; Li, Bing; Li, Wenguo et al. (2014) Transcriptional repression by the BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells. Stem Cell Reports 3:460-74
Singh, Ajeet Pratap; Archer, Trevor K (2014) Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation. Nucleic Acids Res 42:2958-75
Singh, Ajeet Pratap; Cummings, Connie A; Mishina, Yuji et al. (2013) SOX8 regulates permeability of the blood-testes barrier that affects adult male fertility in the mouse. Biol Reprod 88:133
Jefferson, Wendy N; Chevalier, Dominique M; Phelps, Jazma Y et al. (2013) Persistently altered epigenetic marks in the mouse uterus after neonatal estrogen exposure. Mol Endocrinol 27:1666-77

Showing the most recent 10 out of 61 publications