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 [1], [2], [3].

Receptors heterodimers bind retinoid ligands. This interaction is facilitated by Cellular retinoic acid binding protein 2 (CRABP2) and is stabilized by Cyclin D3 [4], [5].

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) [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. 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 [13], [17].

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 [18], [19], [20], [21], [22], [23], [24], [25], [26], [27].

1. Zhang XK, Pfahl M
   Hetero- and homodimeric receptors in thyroid hormone and vitamin A action. Receptor 1993 Fall;3(3):183-91
2. Rastinejad F, Wagner T, Zhao Q, Khorasanizadeh S
   Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1. The EMBO journal 2000 Mar 1;19(5):1045-54
3. Weston AD, Blumberg B, Underhill TM
   Active repression by unliganded retinoid receptors in development: less is sometimes more. The Journal of cell biology 2003 Apr 28;161(2):223-8
4. Budhu A, Gillilan R, Noy N
   Localization of the RAR interaction domain of cellular retinoic acid binding protein-II. Journal of molecular biology 2001 Jan 26;305(4):939-49
5. Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L
   Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II. The Journal of biological chemistry 2003 Feb 21;278(8):6355-62
6. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG
   A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1996 May 3;85(3):403-14
7. Li H, Gomes PJ, Chen JD
   RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proceedings of the National Academy of Sciences of the United States of America 1997 Aug 5;94(16):8479-84
8. Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG
   Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science (New York, N.Y.) 1998 Jan 30;279(5351):703-7
9. Hong H, Darimont BD, Ma H, Yang L, Yamamoto KR, Stallcup MR
   An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors. The Journal of biological chemistry 1999 Feb 5;274(6):3496-502
10. Leo C, Chen JD
    The SRC family of nuclear receptor coactivators. Gene 2000 Mar 7;245(1):1-11
11. Farboud B, Hauksdottir H, Wu Y, Privalsky ML
    Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression. Molecular and cellular biology 2003 Apr;23(8):2844-58
12. Hu X, Chen Y, Farooqui M, Thomas MC, Chiang CM, Wei LN
    Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation. The Journal of biological chemistry 2004 Jan 2;279(1):319-25
13. Bastien J, Rochette-Egly C
    Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene 2004 Mar 17;328:1-16
14. Jurutka PW, Thompson PD, Whitfield GK, Eichhorst KR, Hall N, Dominguez CE, Hsieh JC, Haussler CA, Haussler MR
    Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4. Journal of cellular biochemistry 2005 Apr 1;94(5):917-43
15. Singh RR, Kumar R
    Steroid hormone receptor signaling in tumorigenesis. Journal of cellular biochemistry 2005 Oct 15;96(3):490-505
16. Tsai LN, Ku TK, Salib NK, Crowe DL
    Extracellular signals regulate rapid coactivator recruitment at AP-1 sites by altered phosphorylation of both CREB binding protein and c-jun. Molecular and cellular biology 2008 Jul;28(13):4240-50
17. Rochette-Egly C, Adam S, Rossignol M, Egly JM, Chambon P
    Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell 1997 Jul 11;90(1):97-107
18. Brousse-Gaury P
    [Sexual activity in females of Periplaneta americana l. (author's transl)]. Bulletin biologique de la France et de la Belgique 1978;112(2):129-65
19. Robyr D, Wolffe AP, Wahli W
    Nuclear hormone receptor coregulators in action: diversity for shared tasks. Molecular endocrinology (Baltimore, Md.) 2000 Mar;14(3):329-47
20. Cohen RN, Putney A, Wondisford FE, Hollenberg AN
    The nuclear corepressors recognize distinct nuclear receptor complexes. Molecular endocrinology (Baltimore, Md.) 2000 Jun;14(6):900-14
21. Ahringer J
    NuRD and SIN3 histone deacetylase complexes in development. Trends in genetics : TIG 2000 Aug;16(8):351-6
22. Guidez F, Petrie K, Ford AM, Lu H, Bennett CA, MacGregor A, Hannemann J, Ito Y, Ghysdael J, Greaves M, Wiedemann LM, Zelent A
    Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood 2000 Oct 1;96(7):2557-61
23. Cohen RN, Brzostek S, Kim B, Chorev M, Wondisford FE, Hollenberg AN
    The specificity of interactions between nuclear hormone receptors and corepressors is mediated by distinct amino acid sequences within the interacting domains. Molecular endocrinology (Baltimore, Md.) 2001 Jul;15(7):1049-61
24. Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB
    Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature 2002 Feb 14;415(6873):813-7
25. Loinder K, Soderstrom M
    Functional analyses of an LXXLL motif in nuclear receptor corepressor (N-CoR). The Journal of steroid biochemistry and molecular biology 2004 Aug;91(4-5):191-6
26. Lee S, Privalsky ML
    Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Molecular endocrinology (Baltimore, Md.) 2005 Apr;19(4):863-78
27. McDonel P, Costello I, Hendrich B
    Keeping things quiet: roles of NuRD and Sin3 co-repressor complexes during mammalian development. The international journal of biochemistry & cell biology 2009 Jan;41(1):108-16