Coactivator function defines the active estrogen receptor alpha cistrome.
Proper activation of transcriptional networks in complex organisms is central to the response to stimuli. We demonstrate that the selective activation of a subset of the estrogen receptor alpha (ERalpha) cistrome in MCF7 breast cancer cells provides specificity to the estradiol (E2) response. ERalpha-specific enhancers that are subject to E2-induced coactivator-associated arginine methyltransferase 1 (CARM1) action are critical to E2-stimulated gene expression. This is true for both FoxA1-dependent and independent enhancers. In contrast, a subset of E2-suppressed genes are controlled by FoxA1-independent ERalpha binding sites. Nonetheless, these are sites of E2-induced CARM1 activity. In addition, the MCF7 RNA polymerase II cistrome reveals preferential occupancy of E2-regulated promoters prior to stimulation. Interestingly, E2-suppressed genes tend to lie in otherwise silent genomic regions. Together, our results suggest that the transcriptional response to E2 in breast cancer cells is dependent on the interplay between polymerase II pre-occupied promoters and the subset of the ERalpha cistrome associated with coactivation.
Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
Mathieu
M
Lupien
Jérôme
J
Eeckhoute
Clifford A
CA
Meyer
Susan A
SA
Krum
Daniel R
DR
Rhodes
X Shirley
XS
Liu
Myles
M
Brown
D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004257:DNA Polymerase II / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism
D047628:Estrogen Receptor alpha; D006657:Histones; D004958:Estradiol; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D004257:DNA Polymerase II