Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters.
In breast cancer and normal estrogen target tissues, estrogen receptor-alpha (ERalpha) signaling results in the establishment of spatiotemporal patterns of gene expression. Whereas primary target gene regulation by ERalpha involves recruitment of coregulatory proteins, coactivators, or corepressors, activation of these downstream promoters by receptor signaling may also involve partnership of ERalpha with other transcription factors. By using an integrated, genome-wide approach that involves ChIP-chip and computational modeling, we uncovered 13 ERalpha-responsive promoters containing both ERalpha and c-MYC binding elements located within close proximity (13-214 bp) to each other. Estrogen stimulation enhanced the c-MYC-ERalpha interaction and facilitated the association of ERalpha, c-MYC, and the coactivator TRRAP with these estrogen-responsive promoters, resulting in chromatin remodeling and increased transcription. These results suggest that ERalpha and c-MYC physically interact to stabilize the ERalpha-coactivator complex, thereby permitting other signal transduction pathways to fine-tune estrogen-mediated signaling networks.
Cheng
Alfred S L
AS
Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA.
Jin
Victor X
VX
Fan
Meiyun
M
Smith
Laura T
LT
Liyanarachchi
Sandya
S
Yan
Pearlly S
PS
Leu
Yu-Wei
YW
Chan
Michael W Y
MW
Plass
Christoph
C
Nephew
Kenneth P
KP
Davuluri
Ramana V
RV
Huang
Tim H-M
TH
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D003198:Computer Simulation; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D047628:Estrogen Receptor alpha; D004967:Estrogens; D014157:Transcription Factors