title: Transcriptional and posttranscriptional regulations of the HLA-G gene.
abstract: HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3' untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3'UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), 18618-970 Botucatu, SP, Brazil.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of São Paulo (USP), 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Veiga-Castelli
authors.affiliation: Alternative Energies and Atomic Energy Commission, Institute of Emerging Diseases and Innovative Therapies, Department of Hematology and Immunology Research, Saint-Louis Hospital, 75010 Paris, France ; Paris-Diderot University, Sorbonne Paris-Cité, UMR E5, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Layale
authors.initials: L
authors.lastname: Yaghi
authors.affiliation: Alternative Energies and Atomic Energy Commission, Institute of Emerging Diseases and Innovative Therapies, Department of Hematology and Immunology Research, Saint-Louis Hospital, 75010 Paris, France ; Paris-Diderot University, Sorbonne Paris-Cité, UMR E5, University Institute of Hematology, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Philippe
authors.identifier: 0000-0002-2868-7401
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of São Paulo (USP), 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D005786:Gene Expression Regulation; D059951:HLA-G Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; D035683:MicroRNAs; D020033:Protein Isoforms; D012333:RNA, Messenger
references.citation: Immunogenetics. 2004 Dec;56(9):657-66
references.pmid: 15578264
references.citation: Cell Mol Life Sci. 2011 Feb;68(3):369-95
references.pmid: 21107637
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16180-5
references.pmid: 12454284
references.citation: Reprod Biomed Online. 2012 Oct;25(4):415-24
references.pmid: 22877943
references.citation: Hum Immunol. 2013 Mar;74(3):383-8
references.pmid: 23220497
references.citation: J Mol Evol. 2001 Dec;53(6):642-50
references.pmid: 11677624
references.citation: Nature. 2003 Apr 17;422(6933):735-8
references.pmid: 12700765
references.citation: Placenta. 1998 Mar-Apr;19(2-3):127-32
references.pmid: 9548178
references.citation: Pharmacogenet Genomics. 2006 Sep;16(9):615-23
references.pmid: 16906016
references.citation: J Immunol. 1994 Dec 15;153(12):5516-24
references.pmid: 7989753
references.citation: Genes Immun. 2010 Mar;11(2):134-41
references.pmid: 19798077
references.citation: Hum Immunol. 2006 Jan-Feb;67(1-2):53-62
references.pmid: 16698426
references.citation: Immunogenetics. 1990;31(4):245-52
references.pmid: 1691737
references.citation: Int J Cancer. 2005 Mar 1;113(6):928-36
references.pmid: 15514928
references.citation: Immunogenetics. 2004 Jun;56(3):135-41
references.pmid: 15133645
references.citation: PLoS One. 2013 Oct 25;8(10):e71742
references.pmid: 24204558
references.citation: Blood. 2004 Nov 15;104(10):3153-60
references.pmid: 15284117
references.citation: Hum Reprod. 2006 Jul;21(7):1743-8
references.pmid: 16501035
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11568-72
references.pmid: 8265591
references.citation: J Immunol. 1991 Oct 1;147(7):2384-90
references.pmid: 1717558
references.citation: Nature. 2012 Nov 1;491(7422):56-65
references.pmid: 23128226
references.citation: Cell Mol Life Sci. 2001 Nov;58(12-13):1943-9
references.pmid: 11766889
references.citation: Int Immunol. 1999 May;11(5):803-11
references.pmid: 10330285
references.citation: Proc Natl Acad Sci U S A. 1987 Dec;84(24):9145-9
references.pmid: 3480534
references.citation: Immunology. 2004 Jan;111(1):53-65
references.pmid: 14678199
references.citation: Tissue Antigens. 2012 May;79(5):326-32
references.pmid: 22489942
references.citation: Infect Genet Evol. 2013 Jun;16:263-9
references.pmid: 23499774
references.citation: Hum Immunol. 2000 Nov;61(11):1086-94
references.pmid: 11137211
references.citation: Immunogenetics. 2001 Oct;53(8):617-25
references.pmid: 11797094
references.citation: Nature. 1997 Sep 25;389(6649):349-52
references.pmid: 9311776
references.citation: Hum Immunol. 2003 Nov;64(11):1057-63
references.pmid: 14602236
references.citation: Immunity. 1997 May;6(5):601-11
references.pmid: 9175838
references.citation: Genes Dev. 1998 Mar 1;12(5):599-606
references.pmid: 9499396
references.citation: Tissue Antigens. 2010 Mar;75(3):253-61
references.pmid: 20070604
references.citation: Hum Immunol. 2007 Apr;68(4):277-85
references.pmid: 17400064
references.citation: Genes Immun. 2013 Dec;14(8):518-26
references.pmid: 24089150
references.citation: Tissue Antigens. 2007 Mar;69(3):255-60
references.pmid: 17493150
references.citation: Immunogenetics. 2007 May;59(5):359-66
references.pmid: 17333165
references.citation: FASEB J. 2013 Aug;27(8):2977-87
references.pmid: 23592762
references.citation: J Immunol. 2009 Dec 1;183(11):6948-59
references.pmid: 19890057
references.citation: J Biol Chem. 2001 Mar 2;276(9):6133-9
references.pmid: 11087747
references.citation: J Immunol. 1993 Oct 1;151(7):3638-45
references.pmid: 8376798
references.citation: Semin Cancer Biol. 1999 Feb;9(1):55-9
references.pmid: 10092551
references.citation: J Reprod Immunol. 2004 Oct;63(2):85-95
references.pmid: 15380940
references.citation: Hum Reprod. 2006 Jan;21(1):46-51
references.pmid: 16210391
references.citation: J Biol Chem. 1995 Feb 24;270(8):3965-73
references.pmid: 7533158
references.citation: Diabetes. 2006 May;55(5):1214-22
references.pmid: 16644675
references.citation: Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Dec 18;38(6):597-602
references.pmid: 17173079
references.citation: Methods Mol Biol. 2006;342:129-38
references.pmid: 16957372
references.citation: Tissue Antigens. 2000 Sep;56(3):232-9
references.pmid: 11034559
references.citation: Nucleic Acids Res. 2012 Nov;40(21):10742-52
references.pmid: 23002136
references.citation: Immunogenetics. 1993;38(2):117-30
references.pmid: 7683306
references.citation: Transplantation. 2007 Jul 27;84(2):231-7
references.pmid: 17667815
references.citation: Hum Immunol. 2000 Sep;61(9):863-6
references.pmid: 11053629
references.citation: Arch Dermatol Res. 2011 Nov;303(9):679-84
references.pmid: 21847675
references.citation: J Rheumatol. 2013 Jul;40(7):1104-13
references.pmid: 23678155
references.citation: Semin Cancer Biol. 2003 Oct;13(5):361-9
references.pmid: 14708716
references.citation: Mod Pathol. 2009 Aug;22(8):1075-82
references.pmid: 19407850
references.citation: Hum Immunol. 1999 Dec;60(12):1237-44
references.pmid: 10626737
references.citation: Tissue Antigens. 1997 Apr;49(4):356-64
references.pmid: 9151387
references.citation: Genes Dev. 1995 May 1;9(9):1021-32
references.pmid: 7744245
references.citation: J Immunol. 1999 Aug 1;163(3):1428-34
references.pmid: 10415043
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: J Immunol. 2012 Apr 15;188(8):3820-8
references.pmid: 22412192
references.citation: Nature. 2003 Sep 18;425(6955):244-5
references.pmid: 13679896
references.citation: Semin Cancer Biol. 2007 Dec;17(6):444-50
references.pmid: 17707652
references.citation: J Clin Endocrinol Metab. 2000 Oct;85(10):3932-6
references.pmid: 11061559
references.citation: Genes Immun. 2014 Mar;15(2):95-106
references.pmid: 24352166
references.citation: Am J Pathol. 2013 Feb;182(2):540-52
references.pmid: 23219427
references.citation: Hum Immunol. 2012 Aug;73(8):811-7
references.pmid: 22651916
references.citation: Ann N Y Acad Sci. 2009 Sep;1173:538-44
references.pmid: 19758196
references.citation: Cell Stress Chaperones. 2000 Jul;5(3):207-18
references.pmid: 11005379
references.citation: Immunogenetics. 1998 Aug;48(3):208-21
references.pmid: 9683666
references.citation: Immunogenetics. 2000 Jan;51(1):50-8
references.pmid: 10663562
references.citation: Hum Immunol. 1998 Dec;59(12):751-7
references.pmid: 9831130
references.citation: Hum Immunol. 2000 Nov;61(11):1138-49
references.pmid: 11137219
references.citation: J Immunol. 1998 Sep 1;161(5):2276-83
references.pmid: 9725221
references.citation: Tissue Antigens. 2001 Jan;57(1):15-21
references.pmid: 11169254
references.citation: Immunity. 1997 May;6(5):591-600
references.pmid: 9175837
references.citation: Tissue Antigens. 2013 Jul;82(1):53-8
references.pmid: 23745572
references.citation: Hum Immunol. 1998 Aug;59(8):524-8
references.pmid: 9712358
references.citation: EMBO J. 1997 Mar 3;16(5):1045-55
references.pmid: 9118943
references.citation: Int J Immunogenet. 2010 Aug;37(4):307-11
references.pmid: 20636826
references.citation: PLoS One. 2012;7(3):e33395
references.pmid: 22438923
references.citation: Hum Immunol. 2009 Dec;70(12):1020-5
references.pmid: 19664672
references.citation: Placenta. 1999 May;20(4):293-301
references.pmid: 10329350
references.citation: J Immunol. 1995 Apr 1;154(7):3283-99
references.pmid: 7897212
references.citation: Tissue Antigens. 2008 Nov;72(5):502-4
references.pmid: 18937797
references.citation: Transplant Proc. 2001 May;33(3):2277-80
references.pmid: 11377528
references.citation: Neoplasma. 2007;54(6):455-62
references.pmid: 17949227
references.citation: Hum Immunol. 2012 Nov;73(11):1140-6
references.pmid: 22922127
references.citation: Hum Immunol. 2003 Nov;64(11):1039-44
references.pmid: 14602233
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13794-9
references.pmid: 20639463
references.citation: Blood. 2002 Jan 15;99(2):609-17
references.pmid: 11781245
references.citation: Hum Immunol. 1997 Jan;52(1):41-6
references.pmid: 9021408
references.citation: Am J Hum Genet. 2005 Feb;76(2):349-57
references.pmid: 15611928
references.citation: Immunity. 1998 Oct;9(4):531-41
references.pmid: 9806639
references.citation: J Immunol. 2005 Oct 15;175(8):4866-74
references.pmid: 16210588
references.citation: Hum Immunol. 2013 Apr;74(4):478-82
references.pmid: 23261410
references.citation: J Biol Chem. 1997 Oct 31;272(44):27549-57
references.pmid: 9346889
references.citation: Tissue Antigens. 2012 Sep;80(3):259-62
references.pmid: 22775767
references.citation: J Immunol. 2001 Nov 1;167(9):5175-84
references.pmid: 11673530
references.citation: J Biol Chem. 2006 Apr 14;281(15):10439-47
references.pmid: 16455647
references.citation: Proc Natl Acad Sci U S A. 1992 May 1;89(9):3947-51
references.pmid: 1570318
references.citation: Immunogenetics. 1997;45(6):464-5
references.pmid: 9089111
references.citation: Immunogenetics. 2003 May;55(2):63-79
references.pmid: 12712263
references.citation: J Immunol. 1993 Sep 1;151(5):2633-45
references.pmid: 8360483
references.citation: Science. 1990 Apr 13;248(4952):220-3
references.pmid: 2326636
references.citation: Tissue Antigens. 2013 Oct;82(4):286-7
references.pmid: 24032992
references.citation: J Biol Chem. 2002 Oct 18;277(42):39525-31
references.pmid: 12183445
references.citation: Pharmacol Ther. 2008 Jan;117(1):94-104
references.pmid: 17928059
references.citation: Infect Genet Evol. 2013 Jul;17:1-7
references.pmid: 23541412
references.citation: Hum Immunol. 2003 Nov;64(11):1005-10
references.pmid: 14602228
references.citation: Transplant Proc. 1999 Jun;31(4):1857-9
references.pmid: 10371973
references.citation: J Invest Dermatol. 2005 Dec;125(6):1139-48
references.pmid: 16354183
references.citation: Int J Immunogenet. 2014 Feb;41(1):29-33
references.pmid: 23829564
references.citation: Hum Mol Genet. 1993 Dec;2(12):2200
references.pmid: 8111399
references.citation: Am J Hum Genet. 2003 Jun;72(6):1425-35
references.pmid: 12721954
references.citation: J Reprod Immunol. 1999 Jan;42(1):1-15
references.pmid: 10098828
references.citation: Hum Reprod. 2006 Oct;21(10):2538-44
references.pmid: 16684846
references.citation: J Clin Invest. 2004 Sep;114(6):744-54
references.pmid: 15372095
references.citation: Hum Immunol. 1999 Nov;60(11):1113-8
references.pmid: 10600009
references.citation: Hum Immunol. 2013 Apr;74(4):473-7
references.pmid: 23228392
references.citation: Transpl Immunol. 2009 Mar;20(4):229-31
references.pmid: 19038339
references.citation: Endocrinology. 2006 Apr;147(4):1780-8
references.pmid: 16439450
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6330-4
references.pmid: 9177217
references.citation: Front Immunol. 2011 Oct 04;2:48
references.pmid: 22566838
references.citation: Sci STKE. 2005 Oct 18;2005(306):re12
references.pmid: 16234508
references.citation: Mol Hum Reprod. 2008 Nov;14(11):649-53
references.pmid: 18952696
references.citation: Biochim Biophys Acta. 2010 Feb;1802(2):292-300
references.pmid: 19897031
references.citation: EMBO J. 1986 Dec 20;5(13):3553-62
references.pmid: 3030732
references.citation: Tissue Antigens. 1999 Jan;53(1):1-13
references.pmid: 10082426
references.citation: Mol Biol Evol. 2011 Nov;28(11):3069-86
references.pmid: 21622995
references.citation: Immunol Today. 1998 Jul;19(7):308-12
references.pmid: 9666603
references.citation: Tissue Antigens. 2004 Jul;64(1):66-9
references.pmid: 15191524
references.citation: Mol Biol Evol. 2013 Nov;30(11):2423-34
references.pmid: 23945036
references.citation: Am J Hum Genet. 2007 Oct;81(4):829-34
references.pmid: 17847008
references.citation: J Exp Med. 1994 Dec 1;180(6):2371-6
references.pmid: 7964510
references.citation: Hum Immunol. 2002 Jun;63(6):495-501
references.pmid: 12039526
references.citation: Nat Rev Genet. 2003 Aug;4(8):626-37
references.pmid: 12897774
references.citation: Tissue Antigens. 2012 Apr;79(4):272-8
references.pmid: 22283419
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D140-4
references.pmid: 16381832
references.citation: Hum Immunol. 2002 May;63(5):405-12
references.pmid: 11975984
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1191-6
references.pmid: 12552087
references.citation: J Exp Med. 1997 Jul 21;186(2):289-98
references.pmid: 9221758
references.citation: Nature. 2011 Apr 28;472(7344):495-8
references.pmid: 21499264
references.citation: J Immunol. 2012 May 15;188(10):4940-50
references.pmid: 22490867
references.citation: Hum Mol Genet. 2005 Dec 1;14(23):3619-28
references.pmid: 16236759
references.citation: J Allergy Clin Immunol. 2013 Jun;131(6):1496-503
references.pmid: 23534973
references.citation: Hum Immunol. 2010 Apr;71(4):428-31
references.pmid: 20085794
references.citation: Int J Immunogenet. 2009 Dec;36(6):361-6
references.pmid: 19821846
references.citation: Blood. 2010 Aug 12;116(6):935-44
references.pmid: 20448110
references.citation: Tissue Antigens. 2007 Oct;70(4):330-4
references.pmid: 17767556
references.citation: Hum Immunol. 2000 Nov;61(11):1102-7
references.pmid: 11137213
references.citation: Genet Mol Biol. 2012 Dec;35(4 (suppl)):919-23
references.pmid: 23412401
references.citation: Hum Immunol. 2013 Feb;74(2):203-6
references.pmid: 23127550
references.citation: Mol Cell Biol. 2000 Oct;20(20):7716-25
references.pmid: 11003667
references.citation: Tissue Antigens. 2013 Nov;82(5):317-26
references.pmid: 24131018
references.citation: Hum Immunol. 2013 Jul;74(7):818-27
references.pmid: 23583363
references.citation: Eur J Immunogenet. 2004 Dec;31(6):275-8
references.pmid: 15548266