ESR1:ESTG and KDM4B bind H3K9me3 target gene enhancers

Stable Identifier
Reaction [binding]
Homo sapiens
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Transcriptional induction of a number of estrogen-responsive genes, including MYC, MYB, GREB1 and KDM4B itself, is dependent on KDM4B-dependent H3K9 promoter/enhancer demethylation. KDM4B interacts with ESR1 and is recruited to estrogen-responsive target gene promoters or enhancers in an estrogen-dependent manner (Kawazu et al, 2011; Gaughan et al, 2013). Depletion of KDM4B in T47D and MCF7 breast cancer cell lines abrogates the proliferative response to estrogen, consistent with its role in driving expression of estrogen-dependent cell cycle regulators like MYC and CCND1 (Kawazu et al, 2011; Yang et al, 2010). KDM4B additionally interacts with the transcriptional activator SMARCA4, and depletion of KDM4B compromises the recruitment of RNA polymerase II to the MYB promoter in T47D cells (Kawazu et al, 2011). KDM4B is highly expressed in ER alpha-positive breast cancer and prostate cancer (Gaughan et al, 2013; Coffey et al, 2013). KDM4B may also promote estrogen-responsive signaling by interacting with GATA3 and binding to the enhancers of ESR1and FOXA1 genes (Gaughan et al, 2013).

Literature References
PubMed ID Title Journal Year
23723241 KDM4B is a master regulator of the estrogen receptor signalling cascade

Wade, M, O'Neill, D, Gaughan, L, Stockley, J, Tse, S, Robson, CN, Moore, M, Coffey, K, Rogerson, L, Jones, DL, Wright, J

Nucleic Acids Res. 2013
20682797 The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of estrogen induced growth

Buffa, FM, Turley, H, Ragoussis, J, Gatter, KC, Pike, L, Leek, R, Baban, D, Harris, AL, Jubb, AM, Yang, J

Cancer Res. 2010
21445275 Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development

Okada, H, McQuire, T, Goto, K, Mak, TW, Miyagishi, M, Son, DO, Saso, K, Kawazu, M, Wakeham, A, Tong, KI

PLoS ONE 2011
23435229 The lysine demethylase, KDM4B, is a key molecule in androgen receptor signalling and turnover

Jones, D, Heer, R, Alkharaif, D, Gaughan, L, Stockley, J, Mantilla, A, Coffey, K, Ryan-Munden, C, Rogerson, L, Darby, S, Sahadevan, K, Staller, P, O'Neill, D, Robson, CN

Nucleic Acids Res. 2013
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