Transcription Ligand-Dependent Transcription of Retinoid-Target genes
Ligand Dependent Transcription of Retinoid-Target genes Retinoid receptors are asymmetrically oriented Retinoic acid receptor (RAR)/ RetinoidX receptor (RXR) heterodimers that bind to specific DNA sequences or Retinoic acidresponse elements (RAREs) in the promoters of a large number of retinoid-target genes, , . Receptors heterodimers bind retinoid ligands. This interaction is facilitated byCellular retinoic acid binding protein 2 ( CRABP2 ) and is stabilized by CyclinD3 , . Ligand-bound heterodimers recruit nuclear receptor co-activators, such as Nuclearreceptor coactivators 1, 2 and 3 ( NCOA1 (SRC-1), NCOA2 (GRIP1/TIF2), andNCOA2 (pCIP/SRC3) ), histone methyltransferases and acetyltransferases (CARM1, p300, CBP and PCAF ) , , , , , , , , , , . Thisleads to further chromatin decompaction. Subsequently, retinoid receptors become capableof recruiting the basal transcriptional machinery, including General transcriptionfactors II H, II F, II B, II D, and II A ( TFIIH, TFIIF, TFIIB,TFIID, and TFIIA )) via their association with the mediator complex,Thyroid hormone receptor alpha-associated protein and SRB/MED-containing cofactor complex( TRAP/SMCC complex ). The mediator complex then binds RNA polymerase IIholoenzyme and thus expedites the access of the basal transcriptional machinery to thepromoter , . 26S proteasome system regulates the magnitude and duration of theretinoid-mediated transcription. In the absence of the ligand, the DNA-bound heterodimer RAR-alpha/RXR-alpha can repress their targets by recruiting co-repressor supercomplexescontaining Histone deacetylase class I complex, Sin3 complex and co-repressorsNuclear receptor co-repressor 1 and 2 ( N-CoR and SMRT ). Sin3 complexcontains Sin3A-associated protein 18kDa, 30kDa and 130kDa ( SAP18, SAP30and SAP130 )), and SIN3 homolog A ( Sin3a ), as well as several othersubunits , , , , , , , , , .