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Expression Regulation of Major Histocompatibility Complex Class I and Class II Encoding Genes

By Peter J. van den Elsen


Major histocompatibility complex (MHC)-I and MHC-II molecules play an essential role in the immune response to pathogens by virtue of their ability to present peptides to CD8+ and CD4+ T cells, respectively. Given this critical role, MHC-I and MHC-II genes are regulated in a tight fashion at the transcriptional level by a variety of transcription factors that interact with conserved cis-acting regulatory promoter elements. In addition to the activities of these regulatory factors, modification of chromatin also plays an essential role in the efficient transcription of these genes to meet with local requirement for an effective immune response. The focus of this review is on the transcription factors that interact with conserved cis-acting promoter elements and the epigenetic mechanisms that modulate induced and constitutive expression of these MHC genes

Topics: Immunology
Publisher: Frontiers Research Foundation
OAI identifier: oai:pubmedcentral.nih.gov:3342053
Provided by: PubMed Central
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    1. (1998). A gene encoding a novel RFXassociated transactivator is mutated in the majority of MHC class II deficiency patients.
    2. (1995). A novel DNAbinding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).
    3. (1999). A novel element and a TEF-2-like element activate the major histocompatibility complex class II transactivator in B-lymphocytes.
    4. (2007). A role for EZH2 in silencing of IFN-gamma inducible MHC2TA transcription in uveal melanoma.
    5. (1998). Absence of MHC class II antigen expression in trophoblast cells results from a lack of class II transactivator (CIITA) gene expression.
    6. (2000). Acetylation by PCAF enhances CIITA nuclear accumulationandtransactivationof major histocompatibility complex class II genes.
    7. (2002). Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III.
    8. (2000). Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors.
    9. and Seliger,B.(2008).Lossof interferongamma inducibility of the MHC class II antigen processing pathway in head and neck cancer: evidence for post-transcriptional as well as epigenetic regulation.
    10. (2010). Association of the 19S proteasomalATPases with the ATPase-binding domain of CIITA is essential for CIITA stability and MHC class II expression.
    11. (2006). B cell differentiation controls CIITA promoter accessibility.
    12. (2000). BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells.
    13. (2003). Chromatin remodeling and extragenic transcription at the MHC class II locus control region.
    14. (2000). CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex.
    15. (2003). Class II transactivator (CIITA) promoter methylation does notcorrelatewithsilencingof CIITA transcription in trophoblasts.
    16. (1999). classical and non-classical HLA class I genes through the interferon-stimulated response element.
    17. (1993). Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or barelymphocytesyndrome).Cell 75,
    18. (2007). Constitutive and IFNgamma-induced activation of MHC2TA promoter type III in human melanoma cell lines is governed by separate regulatory elements within the PIII upstream regulatoryregion.Mol.Immunol.44,
    19. (2002). CREB provides for an alternative pathway of HLAGtransactivation.J.Biol.Chem.277,
    20. (1999). CREB regulates MHC class II expression in a CIITAdependent manner.
    21. (2010). CTCF controls expression and chromatin architecture of the human major histocompatibility complex class II locus.
    22. (2002). Cutting edge: CATERPILLER: a large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains.
    23. (1994). Developmental extinction of major histocompatibility complex class II gene expression in plasmocytes is mediated by silencing of the transactivator gene CIITA.
    24. (2002). DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.
    25. (2004). E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivatorpromoterIII(CIITA-PIII).Blood 104,
    26. (2011). Early epigenetic events regulate the adaptive immune response gene CIITA.
    27. (2005). Epigenetic control of MHC-II: interplay between CIITA and histonemodifying enzymes.
    28. (2004). Epigenetic inactivation of class II transactivator (CIITA) is associated with the absence of interferon-gammainduced HLA-DR expression in colorectal and gastric cancer cells.
    29. (2006). Epigenetic silencing of MHC2TA transcription
    30. (2011). Epigeneticregulationof CIITAexpression inhumanT-cells.Biochem.Pharmacol. PMID: 21664896. [Epub ahead of print].
    31. (1997). Expression of MHC class II molecules in different cellular and functional compartments is controlled bydifferentialusageof multiplepromoters of the transactivator CIITA.
    32. (2011). Expression regulation of major histocompatibility complex class I and class II encoding genes.
    33. (1997). Formation of a regulatory factor X/X2 box-binding protein/nuclear factor-Y multiproteincomplexontheconservedregulatory regions of HLA class II genes.
    34. (2007). genes for de novo methylation in cancer.
    35. (2009). Genetic and epigenetic control of the major histocompatibility complex class Ib gene HLA-G in trophoblast cell lines.
    36. (2009). HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages andsmoothmusclecells.J.Mol.Cell.
    37. (2005). Histone acetylation regulates the cell type specific CIITA promoters, MHC class II expression and antigen presentation in tumor cells.
    38. (2003). Histone deacetylase 1/mSin3A disrupts gamma interferon-induced CIITA function and major histocompatibility complex class II enhanceosome formation.
    39. (2003). Histone deacetylation, but not hypermethylation, modifies class II transactivator and MHC class II gene expressioninsquamouscellcarcinomas.
    40. (2003). HLA-G gene repression is reversed by demethylation.Proc.Natl.Acad.Sci.U.S.A.100,
    41. (2004). Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-gamma in haematopoietic tumour cells.
    42. (1999). Interactions between the class II transactivator and CREB binding protein increase transcriptionof majorhistocompatibility complex class II genes.
    43. (2002). Interferongamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent.
    44. (2005). Interplay among coactivator-associated arginine methyltransferase 1, CBP, andCIITAinIFN-gamma-inducible MHC-II gene expression.
    45. (1998). Involvement of CREB binding protein in expression of major histocompatibilitycomplexclassIIgenesviainteraction with the class II transactivator.
    46. (2002). Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation.
    47. (2000). Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells and is caused by methylation of the IFN-gamma inducible promoter (PIV) of CIITA.
    48. (1999). Lack of class II transactivator causes severe defi-ciency of HLA-DR expression in small cell lung cancer.
    49. (2003). Locus-specific constitutive and cytokine induced HLA class I gene expression.
    50. (2004). Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITA.
    51. M.,andVan den Elsen,P.J.(2001).TheMHC-specific enhanceosome and its role in MHC class I and beta(2)-microglobulin gene transactivation.
    52. M.,Van derStoep,N.,andBoss,J.M.(2003). DNA methylation and expression of major histocompatibility complex class I and class II transactivator genes in human developmental tumor cells and in T cell malignancies.
    53. (2002). Major histocompatibility complex class II transcriptional platform: assembly of nuclear factor Y and regulatory factor X (RFX)
    54. (2001). Maturation of dendritic cells is accompanied by rapid transcriptionalsilencingof classIItransactivator (CIITA) expression.
    55. (2008). Methylation of CIITA promoter IV causes loss of HLAII inducibility by IFN-gamma in promyelocytic cells.
    56. (2000). Methylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control.
    57. (2003). MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators?
    58. (2010). NLR family member NLRC5 is a transcriptional regulator of MHC class I genes.
    59. (2008). NLRs at the intersection of cell death and immunity.
    60. (2011). paper pending published: 13
    61. (2010). Phosphorylation and ubiquitination of degron proximal residues are essential for class II transactivator (CIITA) transactivation and major histocompatibility classIIexpression.J.Biol.Chem.285,
    62. (2011). Positive regulatory domain I (PRDM1) and IRF8/PU.1 counter-regulate MHC class II transactivator (CIITA) expression during dendritic cell maturation.
    63. (2001). Positive regulatory domain I binding factor 1 silences class II transactivator expression in multiple myeloma cells.
    64. (2007). Positive regulatory domain I-binding factor 1 mediates repression of the MHC class II transactivator (CIITA) type IV promoter.
    65. (2009). Reduced human leukocyte antigen expression in advanced-stage Ewing sarcoma: implications for immune recognition.
    66. (2002). Regulation and specificity of MHC2TApromoterusageinhuman primaryTlymphocytesandcellline.
    67. (2008). Regulation of acetylation at the major histocompatibility complex class II proximal promoter by the 19S proteasomal ATPase Sug1.
    68. (2011). Regulation of major histocompatibility complex class II genes.
    69. Regulation of MHC class II expression in human T-cell malignancies.
    70. (1999). RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency.
    71. (1997). RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.
    72. (2010). Roles for common MLL/COMPASS subunits and the 19S proteasome in regulating CIITA pIV and MHC class II gene expression and promoter methylation.
    73. (2009). RREB-1 is a transcriptional repressor of HLA-G.
    74. (1997). Site alpha is crucial for two routes of IFN gamma-induced MHC class Itransactivation:theISRE-mediated route and a novel pathway involving CIITA.
    75. Skinner,C.A.,Dey,A.,Ozato,K.,and Ting,J.P.(1997).Inductionof MHC class I expression by the MHC class IItransactivatorCIITA.Immunity 6,
    76. (2008). Spatial distribution of histone methylation during MHC class II expression.
    77. (2000). Synergistic induction of HLA class I expression by RelA and CIITA.
    78. (2008). The 19S proteasome ATPase Sug1 plays a critical role in regulating MHC class II transcription.
    79. (2010). The 19SATPaseS6a(S6 /TBP1)regulates the transcription initiation of class II transactivator.
    80. (2008). The chromatin-remodeling enzyme BRG1 coordinates CIITA induction through many interdependent distal enhancers.
    81. (2002). The class II transactivator requires brahma-related gene 1 to activate transcriptionof majorhistocompatibility complex class II genes.
    82. (2006). The human major histocompatibility complex class II HLA-DRB1 and HLA-DQA1 genes are separated by a CTCF-binding enhancer-blocking element.
    83. (2008). The insulator factor CTCF controls MHC class II gene expression and is required for the formation of longdistance chromatin interactions.
    84. (1999). The regulation of HLA class I expression: is HLA-G the odd one out?
    85. (1998). The role of enhancer A in the locus-specific transactivation of classical and non-classical MHC class I genes by NF-κB.
    86. (2001). Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250.
    87. (2004). Transcriptional regulation of antigen presentation.
    88. (2000). Transcriptional scaffold: CIITA interacts with NF-Y, RFX, and CREB to cause stereospecific regulation of the class II major histocompatibility complex promoter.
    89. (2000). Transcriptionalrepressionbyblimp1 (PRDI-BF1) involves recruitment of histone deacetylase.
    90. (1999). Two distinct gamma interferon-inducible promoters of the major histocompatibility complex class II transactivator gene are differentially regulated by STAT1, interferon regulatory factor 1, and transforming growth factor beta.
    91. (2005). X box-likesequencesintheMHCclass II region maintain regulatory function.

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