Ligand Dependent Transcription of Retinoid-Target
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
, , .
Receptors heterodimers bind retinoid ligands. This interaction is facilitated by
Cellular retinoic acid binding protein 2 (CRABP2) and is
stabilized by Cyclin D3 , .
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
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
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 , , , , , , , , , .
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