scholarly journals The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes

2002 ◽  
Vol 22 (14) ◽  
pp. 5019-5026 ◽  
Author(s):  
Rajini Mudhasani ◽  
Joseph D. Fontes
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Line ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Related Gene ◽  
Class Ii Transactivator ◽  
Atpase Subunit ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Genes

ABSTRACT The class II transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class II genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids 1 to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.

scholarly journals An Isotype-specific Activator of Major Histocompatibility Complex (MHC) Class II Genes That Is Independent of Class II Transactivator

1997 ◽  
Vol 185 (11) ◽  
pp. 1885-1895 ◽  
Author(s):  
John Douhan ◽  
Rebecca Lieberson ◽  
Joan H.M. Knoll ◽  
Hong Zhou ◽  
Laurie H. Glimcher
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Line ◽  
Mhc Class Ii ◽  
Ectopic Expression ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Class Ii Transactivator ◽  
Histocompatibility Complex ◽  
Hla Dr ◽  
Hla Dq

Patients with one type of major histocompatibility complex class II combined immunodeficiency have mutations in a gene termed class II transactivator (CIITA), which coordinately controls the transcription of the three major human class II genes, HLA-DR, -DQ, and -DP. However, the experimentally derived B-lymphoblastoid cell line, clone 13, expresses high levels of HLADQ in the absence of HLA-DR and HLA-DP, despite its mapping by complementation analysis to this group. It was possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA-DQ, but not HLA-DR or -DP transcription. Alternatively, another factor, distinct from CIITA, might control HLA-DQ expression. We report here that ectopic expression of CIITA cDNAs derived by reverse transcriptase polymerase chain reaction from clone 13 do not restore expression of HLA-DQ in another CIITA-deficient cell line, RJ2.2.5. In addition, no CIITA protein is detectable in clone 13 nuclear extracts. In contrast, somatic cell fusion between clone 13 and RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB gene. Taken together, these data demonstrate the existence of an HLA-DQ isotype-specific trans-acting factor, which functions independently of CIITA.

scholarly journals Interferon (IFN) beta acts downstream of IFN-gamma-induced class II transactivator messenger RNA accumulation to block major histocompatibility complex class II gene expression and requires the 48-kD DNA-binding protein, ISGF3-gamma.

1995 ◽  
Vol 182 (5) ◽  
pp. 1517-1525 ◽  
Author(s):  
H T Lu ◽  
J L Riley ◽  
G T Babcock ◽  
M Huston ◽  
G R Stark ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Messenger Rna ◽  
Class Ii ◽  
Type I ◽  
Major Histocompatibility ◽  
Mrna Accumulation ◽  
Class Ii Transactivator ◽  
Ifn Gamma ◽  
Histocompatibility Complex

Interferon (IFN) gamma, a cardinal proinflammatory cytokine, induces expression of the gene products of the class II locus of the major histocompatibility complex (MHC), whereas IFN-alpha or -beta suppresses MHC class II expression. The mechanism of IFN-beta-mediated MHC class II inhibition has been unclear. Recently, a novel factor termed class II transactivator (CIITA) has been identified as essential for IFN-gamma-induced MHC class II transcription. We studied the status of IFN-gamma-induced CIITA messenger RNA (mRNA) accumulation and CIITA-driven transactivation in IFN-beta-treated cells and used cell lines that had defined defects in the type I IFN response pathway to address the roles of IFN signaling components in the inhibition of MHC class II induction. IFN-beta treatment did not suppress IFN-gamma-induced accumulation of CIITA mRNA. After cells were stably transfected with CIITA, endogenous MHC class II genes were constitutively expressed, and MHC class II promoters, delivered by transfection, were actively transcribed in CIITA-expressing cells. Expression of these promoters was significantly impaired by pretreatment with IFN-beta. These results suggest that IFN-beta acts downstream of CIITA mRNA accumulation, and acts in part by reducing the functional competence of CIITA for transactivating MHC class II promoters. IFN stimulated gene factor 3 (ISGF3) gamma was essential for IFN-beta to mediate inhibition of MHC class II induction, regardless of whether MHC class II transcription was stimulated by IFN-gamma or directly by CIITA expression. Results of these experiments suggest that inhibition of MHC class II in IFN-beta-treated cells requires expression of gene(s) directed by the ISGF3-IFN-stimulated response element pathway, and that these gene product(s) may act by blocking CIITA-driven transcription of MHC class II promoters.

scholarly journals Within-trio tests provide little support for post-copulatory selection on major histocompatibility complex haplotypes in a free-living population

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202862
Author(s):  
W. Huang ◽  
J. M. Pemberton
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Ovis Aries ◽  
Transmission Ratio Distortion ◽  
Transmission Ratio ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ratio Distortion ◽  
Mhc Class Ii Genes

Sexual selection has been proposed as a force that could help maintain the diversity of major histocompatibility complex (MHC) genes in vertebrates. Potential selective mechanisms can be divided into pre-copulatory and post-copulatory, and in both cases, the evidence for occurrence is mixed, especially in natural populations. In this study, we used a large number of parent-offspring trios that were diplotyped for MHC class II genes in a wild population of Soay sheep ( Ovis aries ) to examine whether there was within-trio post-copulatory selection on MHC class II genes at both the haplotype and diplotype levels. We found there was transmission ratio distortion of one of the eight MHC class II haplotypes (E) which was transmitted less than expected by fathers, and transmission ratio distortion of another haplotype (A) which was transmitted more than expected by chance to male offspring. However, in both cases, these deviations were not significant after correction for multiple tests. In addition, we did not find any evidence of post-copulatory selection at the diplotype level. These results imply that, given known parents, there is no strong post-copulatory selection on MHC class II genes in this population.

scholarly journals Developmental extinction of major histocompatibility complex class II gene expression in plasmocytes is mediated by silencing of the transactivator gene CIITA.

1994 ◽  
Vol 180 (4) ◽  
pp. 1329-1336 ◽  
Author(s):  
P Silacci ◽  
A Mottet ◽  
V Steimle ◽  
W Reith ◽  
B Mach
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
B Lymphocytes ◽  
Mhc Class Ii ◽  
Plasma Cells ◽  
Terminal Differentiation ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Genes

Constitutive major histocompatibility complex (MHC) class II gene expression is tightly restricted to antigen presenting cells and is under developmental control. Cells of the B cell lineage acquire the capacity to express MHC class II genes early during ontogeny and lose this property during terminal differentiation into plasma cells. Cell fusion experiments have suggested that the extinction of MHC class II expression in plasma cells is due to a dominant repression, but the underlying mechanisms are not understood. CIITA was recently identified as an MHC class II transactivator that is essential for MHC class II expression in B lymphocytes. We show here that inactivation of MHC class II genes in plasmocytes is associated with silencing of the CIITA gene. Moreover, experimentally induced expression of CIITA in plasmocytes leads to reexpression of MHC class II molecules to the same level as that observed on B lymphocytes. We therefore conclude that the loss of MHC class II expression observed upon terminal differentiation of B lymphocytes into plasmocytes results from silencing of the transactivator gene CIITA.

scholarly journals A Mechanism for the Major Histocompatibility Complex–linked Resistance to Autoimmunity

1997 ◽  
Vol 186 (7) ◽  
pp. 1059-1075 ◽  
Author(s):  
Dennis Schmidt ◽  
Joan Verdaguer ◽  
Nuzhat Averill ◽  
Pere Santamaria
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Pancreatic Beta Cell ◽  
Nod Mice ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Nonobese Diabetic ◽  
Histocompatibility Complex ◽  
Nonobese Diabetic Mice ◽  
Mhc Class Ii Genes

Certain major histocompatibility complex (MHC) class II haplotypes encode elements providing either susceptibility or dominant resistance to the development of spontaneous autoimmune diseases via mechanisms that remain undefined. Here we show that a pancreatic beta cell–reactive, I-Ag7–restricted, transgenic TCR that is highly diabetogenic in nonobese diabetic mice (H-2g7) undergoes thymocyte negative selection in diabetes-resistant H-2g7/b, H-2g7/k, H-2g7/q, and H-2g7/nb1 NOD mice by engaging antidiabetogenic MHC class II molecules on thymic bone marrow–derived cells, independently of endogenous superantigens. Thymocyte deletion is complete in the presence of I-Ab, I-Ak + I-Ek or I-Anb1 + I-Enb1 molecules, partial in the presence of I-Aq or I-Ak molecules alone, and absent in the presence of I-As molecules. Mice that delete the transgenic TCR develop variable degrees of insulitis that correlate with the extent of thymocyte deletion, but are invariably resistant to diabetes development. These results provide an explanation as to how protective MHC class II genes carried on one haplotype can override the genetic susceptibility to an autoimmune disease provided by allelic MHC class II genes carried on a second haplotype.

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