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Related Articles Estrogen receptor [beta] binds to and regulates three distinct classes of target genes.
J Biol Chem. 2010 Apr 19;
Authors: Vivar OI, Zhao X, Saunier EF, Griffin C, Mayba OS, Tagliaferri M, Cohen I, Speed TP, Leitman DC
Estrogen receptor [beta] (ER[beta]) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER[beta]-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER[beta] regulates genes, we identified genes regulated by the unliganded and liganded forms of ER[alpha] and ER[beta] in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER[alpha], whereas many genes were regulated by estradiol (E2). These results demonstrate [alpha] requires a ligand to regulate a single class of genes. In contrast, ER[beta] regulated three classes of genes. Class I genes were regulated primarily by unliganded ER[beta]. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER[beta] and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER[beta] regulates different classes of genes ChIP-seq was performed to identify ER[beta] binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER[beta] bound to all three classes of genes demonstrating that ER[beta] binding is not responsible for differential regulation of genes by unliganded and unliganded ER[beta]. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and ligand forms of ER[beta] regulate three classes of genes by interacting with different transcription factors and coactivators.
PMID: 20404318 [PubMed - as supplied by publisher]
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Related Articles Estrogen receptor [beta] binds to and regulates three distinct classes of target genes.
J Biol Chem. 2010 Apr 19;
Authors: Vivar OI, Zhao X, Saunier EF, Griffin C, Mayba OS, Tagliaferri M, Cohen I, Speed TP, Leitman DC
Estrogen receptor [beta] (ER[beta]) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER[beta]-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER[beta] regulates genes, we identified genes regulated by the unliganded and liganded forms of ER[alpha] and ER[beta] in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER[alpha], whereas many genes were regulated by estradiol (E2). These results demonstrate [alpha] requires a ligand to regulate a single class of genes. In contrast, ER[beta] regulated three classes of genes. Class I genes were regulated primarily by unliganded ER[beta]. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER[beta] and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER[beta] regulates different classes of genes ChIP-seq was performed to identify ER[beta] binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER[beta] bound to all three classes of genes demonstrating that ER[beta] binding is not responsible for differential regulation of genes by unliganded and unliganded ER[beta]. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and ligand forms of ER[beta] regulate three classes of genes by interacting with different transcription factors and coactivators.
PMID: 20404318 [PubMed - as supplied by publisher]
More...