title: Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells.
abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators.
authors.affiliation: Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea. Electronic address: kwjeong@gachon.ac.kr.
authors.forename: Kwang Won
authors.initials: KW
authors.lastname: Jeong
mesh_terms: D002843:Chromatin / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D061986:MCF-7 Cells; D008840:Microfilament Proteins / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D002843:Chromatin; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C098179:FLII protein, human; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators
keywords: Chromatin accessibility; Estrogen receptor; FLII; H3K4 methylation; Transcription