Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Taxman, Debra J.; Cressman, Drew E.; Ting, Jenny P.Y.

doi:10.4049/jimmunol.165.3.1410

Cited by 48 publications

(59 citation statements)

References 59 publications

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“…In addition, sensitive real-time RT-PCR data indicate that GM-CSF does not increase DO␤ transcript levels despite increasing DO␣ levels. It has been previously shown that the two chains of DO are differentially regulated, and that in B cells DO␤ expression is influenced by, but not dependent upon, CIITA (26,30). This raises the question of whether DO␣ expressed in the absence, or in excess, of DO␤ can function independently from, or with another partner than, DO␤.…”

Section: Discussionmentioning

confidence: 99%

“…The decrease in relative CLIP/class II levels seen following GM-CSF treatment may reflect a change in DM, Ii, and/or DO expression, and this was tested directly. Expression of both the ␣-and ␤-chains of DM and DO was examined, as, at least in the case of DO, the two chains are known to be regulated distinctly (26). As shown in Fig.…”

Section: Gm-csf Increases Total Protein Levels Of Dr Dm II and Do␣mentioning

confidence: 99%

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Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Hornell

Beresford

Bushey

et al. 2003

The Journal of Immunology

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GM-CSF stimulates the growth and differentiation of hematopoietic progenitors and also affects mature cell function. These effects have led to the use of GM-CSF as a vaccine adjuvant with promising results; however, the mechanisms underlying GM-CSF-mediated immune potentiation are incompletely understood. In this study, we investigated the hypothesis that the immune stimulatory role of GM-CSF is in part due to effects on class II MHC Ag presentation. We find that, in primary human monocytes treated for 24–48 h, GM-CSF increases surface class II MHC expression and decreases the relative level of the invariant chain-derived peptide, CLIP, bound to surface class II molecules. GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16. Furthermore, GM-CSF-treated monocytes are better stimulators in a mixed leukocyte reaction. Additional analyses of the class II pathway revealed that GM-CSF increases total protein and RNA levels of HLA-DR, DM, and DOα. Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF. Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter. Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CIITA.

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Section: Discussionmentioning

confidence: 99%

Section: Gm-csf Increases Total Protein Levels Of Dr Dm II and Do␣mentioning

confidence: 99%

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Hornell

Beresford

Bushey

et al. 2003

The Journal of Immunology

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“…These four boxes are present in a tightly conserved arrangement with respect to orientation and spacing, and they function together as a single composite regulatory unit (1,2). A similar sequence arrangement has been conserved in the promoter regions of the Ii, HLA-DM, and HLA-DO genes (7)(8)(9)(10)(11), which code for proteins implicated in the intracellular traffic and peptide loading of MHCII molecules (12,13). The promoters of MHC class I genes also contain a related regulatory module (14).…”

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confidence: 99%

The S Box of Major Histocompatibility Complex Class II Promoters Is a Key Determinant for Recruitment of the Transcriptional Co-activator CIITA

Mühlethaler-Mottet

Krawczyk

Masternak

et al. 2004

Journal of Biological Chemistry

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Tightly regulated expression of major histocompatibility complex (MHC) class II genes is critical for the immune system. A conserved regulatory module consisting of four cis-acting elements, the W, X, X2 and Y boxes, controls transcription of MHC class II genes. The X, X2, and Y boxes are bound, respectively, by RFX, CREB, and NF-Y to form a MHC class II-specific enhanceosome complex. The latter constitutes a landing pad for recruitment of the transcriptional co-activator CIITA. In contrast to the well defined roles of the X, X2, and Y boxes, the role of the W region has remained controversial. In vitro binding studies have suggested that it might contain a second RFX-binding site. We demonstrate here by means of promoter pull-down assays that the most conserved subsequence within the W region, called the S box, is a critical determinant for tethering of CIITA to the enhanceosome complex. Binding of CIITA to the enhanceosome requires both integrity of the S box and a remarkably stringent spacing between the S and X boxes. Even a 1-2-base pair change in the native S-X distance is detrimental for CIITA recruitment and promoter function. In contrast to current models, binding of RFX to a putative duplicated binding site in the W box is thus not required for either CIITA recruitment or promoter activity. This paves the way for the identification of novel factors mediating the contribution of the S box to the activation of MHC class II promoters.Major histocompatibility complex (MHC) 1 class II molecules are heterodimeric cell surface glycoproteins that present peptides to the antigen receptor (T cell receptor) of CD4 ϩ T cells. Engagement of MHCII-peptide complexes by the T cell receptor is essential for selection of the mature CD4 ϩ T cell repertoire during T cell development in the thymus and for the initiation, propagation, and regulation of adaptive immune responses by mature T cells in the periphery. Because of these key functions in the adaptive immune response, MHCII expression is tightly controlled in a cell type-specific and inducible manner (for reviews see Refs.

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“…In addition to the genes encoding classical MHCII molecules (HLA-DR, -DP and -DQ), CIITA activates the expression of several genes encoding accessory proteins required for MHCIIrestricted antigen-presentation, namely the invariant chain (Ii), HLA-DM and HLA-DO [17][18][19][20]. It also contributes, albeit to a lesser degree, to classical and nonclassical MHCI expression [4,16,21,22].…”

Section: The Specificity Of Ciitamentioning

confidence: 99%

Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

et al. 2004

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The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigations, the major target genes of CIITA remain those implicated in the presentation of antigenic peptides by MHCII molecules. Although other putative target genes have been reported, the contribution of CIITA to their expression remains indirect, controversial or comparatively minor relative to its decisive role as a regulator of MHCII and related genes. Second, the most important parameter dictating MHCII expression is by far the expression pattern of the gene encoding CIITA (MHC2TA). The vast majority of signals that activate or repress MHCII expression under physiological and pathological situations converge on one or more of the three alternative promoters that drive transcription of the MHC2TA gene. In short, with respect to its specificity and its exquisitely controlled pattern of expression, CIITA is by a long stretch the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen-presentation.

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Identification of Class II Transcriptional Activator-Induced Genes by Representational Difference Analysis: Discoordinate Regulation of the DNα/DOβ Heterodimer

Cited by 48 publications

References 59 publications

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

The S Box of Major Histocompatibility Complex Class II Promoters Is a Key Determinant for Recruitment of the Transcriptional Co-activator CIITA

Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

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