NCOA1 binds the ABCA1gene:NR1H2,3:RXR:NR1H2,3 ligands complex

Stable Identifier
R-HSA-9029551
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Synonyms
NCOA1 binds the ABCA1gene:LXR:RXR:LXR ligands complex
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Liver X receptor LXRα (NR1H3) or LXRβ (NR1H2) heterodimerizes with retinoid X receptors (RXR) and binds to LXR-response elements (LXREs) consisting of a direct repeat of the core sequence 5'-AGGTCA-3' separated by 4 nucleotides (DR4) in the DNA of target genes (Wiebel FF & Gustafsson JA 1997). Under basal conditions, the NR1H2,3:RXR heterodimer is bound to a co-repressor complex in the promoter area of the target genes (Jakobsson T et al. 2009). On ligand activation the co-repressor complex dissociates and is replaced by coactivators. Chromatin immunoprecipitation (ChIP) assays showed the oxysterol-induced interaction of the nuclear receptor coactivator 1 (NCOA1, also known as SRC1) and E1A-associated protein p300 (EP300) with the DR-4 element of the ABCA1 gene promoter (Huuskonen J et al. 2004). This study was performed with human embryonic kidney 293T (HEK293) cells stably overexpressing FLAG-tagged LXRα (Huuskonen J et al. 2004). NCOA1 (SRC1) belongs to the family of p160 coactivators which interact directly with nuclear receptors via LXXLL motifs (L indicates leucine; X, any amino acid), and with other members of the p160 coactivator complex via AD1 and AD2 interaction domains (reviewed in: Xu J & Li Q 2003; Xu L et al. 2009). NCOR1 recruits the transcriptional co-activator EP300 (Chan HM & La Thangue NB 2001). NCOA1 and EP300 are thought to induce local changes in the nucleosome structure via co-activator binding activity, acetylation or methylation of histones and other components of the transcription unit (reviewed in Xu J & Li Q 2003; Xu L et al. 2009; Chan HM & La Thangue NB 2001).

Literature References
PubMed ID Title Journal Year
14764426 Role of p160 coactivator complex in the activation of liver X receptor

Huuskonen, J, Fielding, PE, Fielding, CJ

Arterioscler. Thromb. Vasc. Biol. 2004
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