2014
DOI: 10.1016/j.cell.2014.08.027
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Abstract: Summary Enhancers provide critical information directing cell-type specific transcriptional programs, regulated by binding of signal-dependent transcription factors and their associated cofactors. Here we report that the most strongly activated estrogen (E2)-responsive enhancers are characterized by trans-recruitment and in situ assembly of a large 1-2 MDa complex of diverse DNA-binding transcription factors by ERα at ERE-containing enhancers. We refer to enhancers recruiting these factors as mega transcriptio… Show more

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Cited by 174 publications
(188 citation statements)
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References 52 publications
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“…71), thus linking components of the BER and NHEJ pathways. As DNA-PKcs is activated by ERα 72 and is part of a mega transcription factor complex that is assembled at functional ERα enhancers 73 (FIG. 2b), we surmise that a combination therapy that targets the androgen receptor–DNA-PKcs–PARP1 or ERα–DNA-PKcs–PARP1 axis might be useful for the treatment of malignancies that are driven by these hormones.…”
Section: Repair Factors and Transcriptionmentioning
confidence: 99%
See 1 more Smart Citation
“…71), thus linking components of the BER and NHEJ pathways. As DNA-PKcs is activated by ERα 72 and is part of a mega transcription factor complex that is assembled at functional ERα enhancers 73 (FIG. 2b), we surmise that a combination therapy that targets the androgen receptor–DNA-PKcs–PARP1 or ERα–DNA-PKcs–PARP1 axis might be useful for the treatment of malignancies that are driven by these hormones.…”
Section: Repair Factors and Transcriptionmentioning
confidence: 99%
“…Following the generation of transient DNA nicks, the deployment of DNA damage repair proteins ensures timely repair of single- and perhaps even double-strand breaks. In the case of oestrogen receptor-α (ERα)-regulated transcription, ERα participates in the in situ assembly of a mega transcription factor complex at functional enhancers 73 . c | Transcription-induced DNA supercoiling imposes a barrier to transcript elongation and results in Pol II promoter-proximal pausing.…”
Section: Figurementioning
confidence: 99%
“…Several enhancers have been shown to respond to diverse stimuli such as neuronal depolarization 49 or ERa signalling 60 . In a recent report Rosenfeld and colleagues 61 demonstrated that ERa-responsive enhancers are characterized by the recruitment of a complex of transcription factors. The expression of key transcription factors in response to B-RAF activation may be involved in the enhancer activation.…”
Section: E1mentioning
confidence: 99%
“…Data showed that GATA3 mutations were the main somatic event that characterized tumors arising in young women. Some preclinical data suggest that mutations in GATA3 affect ER binding to DNA, promote tumor growth, and may be associated with endocrine resistance [45][46][47] . These findings are extremely important since the worst prognosis in young breast cancer patients has been observed mainly in ER-positive disease, especially luminal B-like tumors 31 .…”
Section: Gene Expression and Genomic Aberrations In Young Women Withmentioning
confidence: 99%