26S proteasome (19S regulator), TFIIA, TFIIB, CBP, PCAF histone acetylase complex, RNA polymerase II, TRIP2, TFIIF, NCOA2 (GRIP1/TIF2), 26S proteasome (20S core), CAK complex, N-CoR, RARalpha, SMRT, SAP30, NCOA1 (SRC1), SAP18, RXRA, RXRA, PKA-cat (cAMP-dependent), TFIIH, PSMC5, RAR-alpha/RXR-alpha, Histone deacetylase class I, SAP130, Sin3A, TFIID, TRAP/SMCC complex , Retinoic acid cytosol, p300, CRABP2, RAR-alpha/RXR-alpha, RARalpha, Cyclin D3, NCOA3 (pCIP/SRC3), CARM1
Ligand Dependent Transcription of Retinoid-Target genes
Retinoid receptors are asymmetrically oriented Retinoic acid receptor (RAR)/ Retinoid X receptor (RXR) heterodimers that bind to specific DNA sequences or Retinoic acid response elements (RAREs) in the promoters of a large number of retinoid-target genes , , .
Ligand-bound heterodimers recruit nuclear receptor co-activators, such as Nuclear receptor coactivators 1, 2 and 3 ( NCOA1 (SRC-1), NCOA2 (GRIP1/TIF2), and NCOA2 (pCIP/SRC3) ), histone methyltransferases and acetyltransferases ( CARM1, p300, CBP and PCAF ) , , , , , , , , , , . This leads to further chromatin decompaction. Subsequently, retinoid receptors become capable of recruiting the basal transcriptional machinery, including General transcription factors 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 II holoenzyme and thus expedites the access of the basal transcriptional machinery to the promoter , .
26S proteasome system regulates the magnitude and duration of the retinoid-mediated transcription.
In the absence of the ligand, the DNA-bound heterodimer RAR-alpha/ RXR-alpha can repress their targets by recruiting co-repressor supercomplexes containing Histone deacetylase class I complex, Sin3 complex and co-repressors Nuclear receptor co-repressor 1 and 2 ( N-CoR and SMRT ). Sin3 complex contains Sin3A-associated protein 18kDa, 30kDa and 130kDa ( SAP18, SAP30 and SAP130 )), and SIN3 homolog A ( Sin3a ), as well as several other subunits , , , , , , , , , .