Genome wide expression analysis of ER alpha and beta with or without E2 treatment in U2OS cell line.

ABSTRACT: Estrogen receptorï?  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 ER 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 liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators. U2OS cell lines are stably transfected with a doxycycline-inducible ER alpha or beta. 18 samples are analyzed with triplicate for each of the 6 conditions. The 6 conditions include ER alpha transfected without doxycycline added, ER alpha transfected with doxycycline added, ER alpha transfected with doxycycline added and E2 treatment, ER beta transfected without doxycycline added, ER beta transfected with doxycycline added, and ER beta transfected with doxycycline added and E2 treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Xiaoyue Zhao 

PROVIDER: E-GEOD-21769 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress