ESR1:ESTG, JUND:FOSB and Cohesin Complex bind distal enhancer elements in MYC gene promoter

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Reaction [binding]
Homo sapiens
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MYC gene expression is estrogen-responsive and expression of MYC and CCND1 contribute to the proliferative response stimulated by estrogen treatment (Dubnik et al, 1987; Dubnik et al, 1988; Dubnik and Shu, 1992; Prall et al, 1998). Estrogen-responsive MYC expression appears to depend at least in part on a distal enhancer element 67 kb from the transcriptional start site that contains a half ERE and an AP-1 site (Denardo et al, 2005; Carroll et al, 2006; Wang et al, 2011). Upon estrogen stimulation, these sites are occupied by ESR1 and a JUND:FOSB heterodimer, respectively (Wang et al, 2011). Estrogen-responsive MYC expression also depends on the cohesin complex, as depletion of the RAD21 cohesin subunit abrogates expression (Stedman et al, 2008; Schmidt et al, 2010; McEwan et al, 2011; Antony et al, 2015). Genome-wide studies have shown that RAD21 and ESR1 binding sites overlap in a fraction of estrogen-responsive genes, including MYC (Schmidt et al, 2010). Cohesin may contribute to target gene expression by promoting chromatin looping structures between distal enhancers and the target gene promoters or through other mechanisms that remain to be elucidated (Li et al, 2012; Antony et al, 2015; reviewed Rhodes et al, 2011; Losada, 2014). Overexpression of histone isoform HIST1H2AC in breast cancer has been shown to contribute to MYC gene expression by promoting the formation of activating chromatin loops and facilitating the recruitment of ESR1, EP300 and RNA polymerase II (Su et al, 2014).

Literature References
PubMed ID Title Journal Year
23145106 Cohesin is required for activation of MYC by estradiol

McEwan, MV, Horsfield, JA, Eccles, MR

PLoS ONE 2012
24854081 Cohesin in cancer: chromosome segregation and beyond

Losada, A

Nat. Rev. Cancer 2014
1630819 Mechanism of estrogen activation of c-myc oncogene expression

Shiu, RP, Dubik, D

Oncogene 1992
25542856 Cohesin modulates transcription of estrogen-responsive genes

McEwan, MV, Horsfield, JA, Antony, J, O'Sullivan, JM, Print, CG, Dasgupta, T, Rhodes, JM

Biochim. Biophys. Acta 2015
15514030 Global gene expression analysis of estrogen receptor transcription factor cross talk in breast cancer: identification of estrogen-induced/activator protein-1-dependent genes

Kim, HT, Cuba, V, Tsimelzon, A, Hilsenbeck, S, Brown, PH, DeNardo, DG

Mol. Endocrinol. 2005
21835891 Estrogen induces c-myc gene expression via an upstream enhancer activated by the estrogen receptor and the AP-1 transcription factor

Wang, C, Kim, H, Mayer, JA, Brown, M, Fertuck, K, Mazumdar, A, Brown, PH

Mol. Endocrinol. 2011
3045126 Transcriptional regulation of c-myc oncogene expression by estrogen in hormone-responsive human breast cancer cells

Shiu, RP, Dubik, D

J. Biol. Chem. 1988
18219272 Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulators

Kissil, JL, Lin, S, Lieberman, PM, Stedman, W, Kang, H, Bartolomei, MS

EMBO J. 2008
3677090 Stimulation of c-myc oncogene expression associated with estrogen-induced proliferation of human breast cancer cells

Dembinski, TC, Shiu, RP, Dubik, D

Cancer Res. 1987
20219941 A CTCF-independent role for cohesin in tissue-specific transcription

Ross-Innes, CS, Hurtado, A, Schwalie, PC, Brown, GD, Flicek, P, Carroll, JS, Odom, DT, Schmidt, D

Genome Res. 2010
22265404 Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation

Wei, CL, Sun, Y, Wang, H, Auerbach, RK, Orlov, YL, Ge, W, Davis, C, Peh, SQ, Mortazavi, A, Sung, WK, Hong, S, Sandhu, KS, Lim, J, Mulawadi, FH, Ong, CT, Wold, B, Li, G, Liu, E, Cheung, E, Goh, Y, Zhang, Z, Zhang, J, Gingeras, T, Euskirchen, G, Poh, HM, Fullwood, MJ, Raha, D, Sim, HS, Snyder, M, Landt, S, Wang, P, Ruan, Y, Fisher-Aylor, KI, Ruan, X, Zheng, M, Gerstein, M

Cell 2012
17013392 Genome-wide analysis of estrogen receptor binding sites

Bekiranov, S, Hall, GF, Li, W, Fertuck, KC, Geistlinger, TR, Sementchenko, V, Liu, XS, Brodsky, AS, Meyer, CA, Silver, PA, Fox, EA, Brown, M, Wang, Q, Keeton, EK, Eeckhoute, J, Song, J, Gingeras, TR, Carroll, JS

Nat. Genet. 2006
21940756 Gene regulation by cohesin in cancer: is the ring an unexpected party to proliferation?

Horsfield, JA, McEwan, M, Rhodes, JM

Mol. Cancer Res. 2011
9671459 c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry

Watts, CK, Prall, OW, Musgrove, EA, Sutherland, RL, Rogan, EM

Mol. Cell. Biol. 1998
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