Mice lacking the transcription factor CIITA--a second look.

Williams, G. Stuart; Malin, Mark; Vremec, David; Chang, Ching-Pin; Boyd, Richard; Benoist, Christophe; Mathis, Diane

doi:10.1093/intimm/10.12.1957

Cited by 88 publications

(87 citation statements)

References 61 publications

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“…The role of CIITA in activating MHC-I genes is thus much less critical than its pivotal function as a transactivator of MHC-II and related genes. This conclusion is consistent with the absence of a marked reduction in MHC-I mRNA or cell surface expression in CIITA-deficient mice [27]. Clearly, MHC-I expression is largely CIITA independent in mice.…”

Section: Discussionsupporting

confidence: 84%

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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CIITA is a master regulatory factor for the expression of MHC class II (MHC-II) and accessory genes involved in Ag presentation. It has recently been suggested that CIITA also regulates numerous other genes having diverse functions within and outside the immune system. To determine whether these genes are indeed relevant targets of CIITA in vivo, we studied their expression in CIITA-transgenic and CIITA-deficient mice. In contrast to the decisive control of MHC-II and related genes by CIITA, nine putative non-MHC target genes (Eif3s2, Kpna6, Tap1, Yars, Col1a2, Ctse, Ptprr, Tnfsf6 and Plxna1) were found to be CIITA independent in all cell types examined. Two other target genes, encoding IL-4 and IFN-c, were indeed found to be up-and down-regulated, respectively, in CIITA-transgenic CD4 + T cells. However, there was no correlation between MHC-II expression and this Th2 bias at the level of individual transgenic T cells, indicating an indirect control by CIITA. These results show that MHC-II-restricted Ag presentation, and its indirect influences on T cells, remains the only pathway under direct control by CIITA in vivo. They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance.

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Section: Discussionsupporting

confidence: 84%

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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show abstract

“…This study, together with other recently reported evidence (21,(32)(33)(34), suggests that, under specific experimental circumstances and in certain cell types, class II may be expressed independently of CIITA. One explanation of our data is that CIITA expression is defective or repressed in MC and Colon 26, and an alternative pathway exists that is activated by DAIs that completely bypasses CIITA.…”

Section: Discussionsupporting

confidence: 82%

Activation of MHC Class I, II, and CD40 Gene Expression by Histone Deacetylase Inhibitors

Magner¹,

Kazim

Stewart

et al. 2000

The Journal of Immunology

265

224

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Epigenetic mechanisms are involved in regulating chromatin structure and gene expression through repression. In this study, we show that histone deacetylase inhibitors (DAIs) that alter the acetylation of histones in chromatin enhance the expression of several genes on tumor cells including: MHC class I, II, and the costimulatory molecule CD40. Enhanced transcription results in a significant increase in protein expression on the tumor cell surface, and expression can be elicited on some tumors that are unresponsive to IFN-γ. The magnitude of induction of these genes cannot be explained by the effect of DAIs on the cell cycle or enhanced apoptosis. Induction of class II genes by DAIs was accompanied by activation of a repressed class II transactivator gene in a plasma cell tumor but, in several other tumor cell lines, class II was induced in the apparent absence of class II transactivator transcripts. These findings also suggest that the abnormalities observed in some tumors in the expression of genes critical to tumor immunity may result from epigenetic alterations in chromatin and gene regulation in addition to well-established mutational mechanisms.

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“…CIITA induces cII expression when ectopically expressed in cII-negative cells, mediates cII-induction by IFN-g, and is defective in a subset of patients with bare lymphocyte syndrome, which is characterized by the absence of cII molecules (Chang and Flavell, 1995;Chang et al, 1994;Mach et al, 1996;Steimle et al, 1993Steimle et al, , 1994. Mice lacking CIITA show defects in both constitutive and IFN-g-inducible cII expression (Chang et al, 1996), although there is detectable cII expression in several cell types (Williams et al, 1998). Although CIITA itself is not a DNA-binding protein, its e ects are mediated through sequences common to all cII promoters, the S, X, X2 and Y motifs (reviewed in Mach et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

Zhu¹,

Pattenden

Bremner

1999

Oncogene

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pRB is required for IFN-g-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRBdependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB +/+ mouse embryonic ®broblasts (MEFs), but de®cient in RB 7/7 MEFs. Inducibility is restored in RB 7/7 MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was speci®cally required for induction of the Ab, but not Aa or other MHC cII genes including Eb, Ii and H2-Ma. Finally, IFN-ginduction of class II transactivator (CIITA), was pRBindependent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

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Mice lacking the transcription factor CIITA--a second look.

Cited by 88 publications

References 61 publications

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Activation of MHC Class I, II, and CD40 Gene Expression by Histone Deacetylase Inhibitors

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

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