Androgen receptor and MYC equilibration centralizes on developmental super-enhancer.
Androgen receptor and MYC equilibration centralizes on developmental super-enhancer.
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雄激素受体和MYC的平衡集中在发育超级增强子上。
DOI：
10.1038/s41467-021-27077-y
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发表时间：
2021-12-15
影响因子：
16.6
通讯作者：
Balk SP
中科院分区：
文献类型：
--
作者：
Guo H;Wu Y;Nouri M;Spisak S;Russo JW;Sowalsky AG;Pomerantz MM;Wei Z;Korthauer K;Seo JH;Wang L;Arai S;Freedman ML;He HH;Chen S;Balk SP
前列腺癌（PCa）中的雄激素受体（AR）可以驱动包括MYC在内的多个基因的转录抑制，并且超生理雄激素在某些患者中有效。在这里，我们表明，这种抑制是独立的AR染色质结合和驱动的共激活子再分配，并通过染色质构象捕获方法显示PCAT 1基因和MYC启动子内的MYC超级增强子之间的相互作用的破坏。相反，雄激素剥夺在体外和体内增加MYC的表达。同时，MYC过表达抑制了整体AR活性，与辅激活因子再分布一致。AR和MYC的这些抑制作用在共享的AR/MYC结合位点处减轻，其也具有显著更高水平的H3 K27乙酰化，表明功能增强子的富集。这些发现表明AR和MYC之间存在复杂的平衡，并表明雄激素剥夺导致MYC增加导致去势抵抗性PCa，而MYC降低可能导致对超生理雄激素治疗的反应。前列腺癌中的雄激素受体（PCa）转录抑制包括MYC在内的多种基因。在这里，作者认为，雄激素剥夺导致MYC增加导致去势抵抗性PCa，而MYC降低可能导致对超生理雄激素治疗的反应。
Androgen receptor (AR) in prostate cancer (PCa) can drive transcriptional repression of multiple genes including MYC, and supraphysiological androgen is effective in some patients. Here, we show that this repression is independent of AR chromatin binding and driven by coactivator redistribution, and through chromatin conformation capture methods show disruption of the interaction between the MYC super-enhancer within the PCAT1 gene and the MYC promoter. Conversely, androgen deprivation in vitro and in vivo increases MYC expression. In parallel, global AR activity is suppressed by MYC overexpression, consistent with coactivator redistribution. These suppressive effects of AR and MYC are mitigated at shared AR/MYC binding sites, which also have markedly higher levels of H3K27 acetylation, indicating enrichment for functional enhancers. These findings demonstrate an intricate balance between AR and MYC, and indicate that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy. Androgen receptor in prostate cancer (PCa) transcriptionally represses multiple genes including MYC. Here, the authors suggest that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy.
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影响因子：
48
作者：
Lareau, Caleb A.;Aryee, Martin J.
通讯作者：
Aryee, Martin J.
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
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影响因子：
64.5
作者：
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Young RA
DOI：
10.1073/pnas.0910668107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Ahmadiyeh, Nasim;Pomerantz, Mark M.;Freedman, Matthew L.
通讯作者：
Freedman, Matthew L.
影响因子：
3.7
作者：
Gao L;Schwartzman J;Gibbs A;Lisac R;Kleinschmidt R;Wilmot B;Bottomly D;Coleman I;Nelson P;McWeeney S;Alumkal J
通讯作者：
Alumkal J