Project description:Mammary epithelial cell line hTert-HME1 was transfected with Control or BRCA2 siRNAs then passaged four times (12 days), then were grown in mammary epithelial growth medium with or without EGF (epithelial growth factor) for 2 passages (6 days).
Project description:Individuals with a single functional copy of the BRCA2 tumor suppressor have elevated risks for breast, ovarian, and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to BRCA2 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function ("BRCA2-crisis"), which may contribute to disease. Here, we establish an in vitro model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These chromatin alterations are reflected in transcriptional profiles of pre-malignant tissues from BRCA2 carriers and, therefore, may reflect natural steps in human disease. By modeling BRCA2-crisis in vitro, we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.
Project description:RAD21 ChIA-PET in human hTERT-HME1 cells For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:Individuals with a single functional copy of the BRCA2 tumor suppressor have elevated risks for breast, ovarian and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to BRCA2 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function (“BRCA2-crisis”), which may contribute to disease. Here we establish an in vitro model for BRCA2-crisis that demonstrates novel epigenetic remodeling and activation of an NF-κB survival pathway in response to transient BRCA2-depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These epigenetic alterations are reflected in transcriptional profiles of pre-malignant tissues from BRCA2-carriers and therefore may reflect natural steps in human disease. By modeling BRCA2-crisis in vitro we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.
Project description:Individuals with a single functional copy of the BRCA2 tumor suppressor have elevated risks for breast, ovarian, and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to BRCA2 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function ("BRCA2-crisis"), which may contribute to disease. Here, we establish an in vitro model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These chromatin alterations are reflected in transcriptional profiles of pre-malignant tissues from BRCA2 carriers and, therefore, may reflect natural steps in human disease. By modeling BRCA2-crisis in vitro, we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.
Project description:Individuals with a single functional copy of the BRCA2 tumor suppressor have elevated risks for breast, ovarian, and other solid tumor malignancies. The exact mechanisms of carcinogenesis due to BRCA2 haploinsufficiency remain unclear, but one possibility is that at-risk cells are subject to acute periods of decreased BRCA2 availability and function ("BRCA2-crisis"), which may contribute to disease. Here, we establish an in vitro model for BRCA2-crisis that demonstrates chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, we identify BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. These chromatin alterations are reflected in transcriptional profiles of pre-malignant tissues from BRCA2 carriers and, therefore, may reflect natural steps in human disease. By modeling BRCA2-crisis in vitro, we have derived insights into pre-neoplastic molecular alterations that may enhance the development of preventative therapies.
Project description:Genome-wide mapping of DNA-methylation in hTert-HME1 cell line treated with control or BRCA2 siRNAs and grown with or without EGF (epithelial growth factor)
Project description:Genome-wide mapping of accessible chromatin in hTert-HME1 cell line treated with control or BRCA2 siRNAs and grown with or without EGF (epithelial growth factor)
Project description:Gene expression profiling by RNA-seq in hTert-HME1 cell line treated with control or BRCA2 siRNAs and grown with or without EGF (epithelial growth factor)
