Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes

Expression of a mammalian major histocompatibility complex (MHC) class I gene is in part regulated by a silencer DNA sequence element which binds a complex of silencer factors. This negative regulatory system is shown to be strikingly similar to the yeast alpha 2 mating-type repression system. A moderate DNA sequence homology exists between the MHC class I silencer DNA element and the yeast alpha 2 operator. Mammalian silencer factors specifically bind to the yeast alpha 2 operator DNA and also specifically interact with a yeast alpha 2-binding protein. Furthermore, the alpha 2 operator functions as a silencer element in mammalian cells when placed upstream of a MHC class I promoter.

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Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

Molecular Biology of the Cell ◽

10.1091/mbc.8.1.47 ◽

1997 ◽

Vol 8 (1) ◽

pp. 47-57 ◽

Cited By ~ 174

Author(s):

E Stang ◽

J Kartenbeck ◽

R G Parton

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Mammalian Cells ◽

Simian Virus 40 ◽

Class I ◽

Major Histocompatibility ◽

Surface Binding ◽

Histocompatibility Complex ◽

Mhc Class I Molecule ◽

Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

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A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

Molecular and Cellular Biology ◽

10.1128/mcb.11.8.4217 ◽

1991 ◽

Vol 11 (8) ◽

pp. 4217-4227 ◽

Cited By ~ 39

Author(s):

J D Weissman ◽

D S Singer

Keyword(s):

Gene Expression ◽

Major Histocompatibility Complex ◽

Mhc Class I ◽

Dna Sequence ◽

Regulatory Element ◽

Class I ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

I Gene ◽

Mhc Class I Gene

A novel regulatory element which contributes to the regulation of quantitative, tissue-specific differences in gene expression has been found between -771 and -676 bp upstream of the major histocompatibility complex (MHC) class I gene, PD1. Molecular dissection of this element reveals the presence of two overlapping functional activities: an enhancer and a silencer. Distinct nuclear factors bind to the overlapping enhancer and silencer DNA sequence elements within the regulatory domain. The levels of factors binding the silencer DNA sequence in different cell types are inversely related to levels of class I expression; in contrast, factors binding the enhancer DNA sequence can be detected in all cells. In cultured cell lines, inhibition of protein synthesis leads to the rapid loss of silencer complexes, with a concomitant increase in both enhancer complexes and MHC class I RNA. From these data, we conclude that a labile silencer factor competes with a constitutively expressed, stable enhancer factor for overlapping DNA-binding sites; the relative abundance of the silencer factor contributes to establishing steady-state levels of MHC class I gene expression.

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A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer

Molecular and Cellular Biology ◽

10.1128/mcb.11.8.4217-4227.1991 ◽

1991 ◽

Vol 11 (8) ◽

pp. 4217-4227 ◽

Cited By ~ 1

Author(s):

J D Weissman ◽

D S Singer

Keyword(s):

Gene Expression ◽

Major Histocompatibility Complex ◽

Mhc Class I ◽

Dna Sequence ◽

Regulatory Element ◽

Class I ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

I Gene ◽

Mhc Class I Gene

A novel regulatory element which contributes to the regulation of quantitative, tissue-specific differences in gene expression has been found between -771 and -676 bp upstream of the major histocompatibility complex (MHC) class I gene, PD1. Molecular dissection of this element reveals the presence of two overlapping functional activities: an enhancer and a silencer. Distinct nuclear factors bind to the overlapping enhancer and silencer DNA sequence elements within the regulatory domain. The levels of factors binding the silencer DNA sequence in different cell types are inversely related to levels of class I expression; in contrast, factors binding the enhancer DNA sequence can be detected in all cells. In cultured cell lines, inhibition of protein synthesis leads to the rapid loss of silencer complexes, with a concomitant increase in both enhancer complexes and MHC class I RNA. From these data, we conclude that a labile silencer factor competes with a constitutively expressed, stable enhancer factor for overlapping DNA-binding sites; the relative abundance of the silencer factor contributes to establishing steady-state levels of MHC class I gene expression.

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Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2015.06.014 ◽

2015 ◽

Vol 167 (3-4) ◽

pp. 166-170

Author(s):

Larissa Sarmento dos Santos ◽

Juliana Pinto da Silva Mol ◽

Auricélio Alves de Macedo ◽

Ana Patrícia Carvalho Silva ◽

Diego Luiz dos Santos Ribeiro ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Brucella Abortus ◽

Class I ◽

Major Histocompatibility ◽

Bovine Placenta ◽

Histocompatibility Complex

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The expression of major histocompatibility complex (MHC) class I antigens in the brain differs markedly in acute and persistent infections with lymphocytic choriomeningitis virus (LCMV)

Journal of Neuroimmunology ◽

10.1016/0165-5728(92)90050-u ◽

1992 ◽

Vol 36 (2-3) ◽

pp. 193-198 ◽

Cited By ~ 31

Author(s):

L. Mucke ◽

M.B.A. Oldstone

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Lymphocytic Choriomeningitis ◽

Lymphocytic Choriomeningitis Virus ◽

Class I ◽

Major Histocompatibility ◽

Persistent Infections ◽

Histocompatibility Complex ◽

Mhc Class I Antigens ◽

The Brain

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Delayed rejection of major histocompatibility complex (MHC) class I and II incompatible skin grafts after Th2 vaccination

Immunology Letters ◽

10.1016/s0165-2478(97)85126-7 ◽

1997 ◽

Vol 56 ◽

pp. 33

Author(s):

A.L.J. Ogilvie ◽

T. Biedermann ◽

C.A. Sander ◽

P.I. Schiller ◽

M. Röcken

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Class I ◽

Skin Grafts ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Delayed Rejection

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Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein

Molecular and Cellular Biology ◽

10.1128/mcb.13.3.1554-1564.1993 ◽

1993 ◽

Vol 13 (3) ◽

pp. 1554-1564

Author(s):

A G Frauman ◽

P Chu ◽

L C Harrison

Keyword(s):

Major Histocompatibility Complex ◽

Beta Cells ◽

Mhc Class I ◽

Pancreatic Beta Cells ◽

Class I ◽

General Mechanism ◽

Major Histocompatibility ◽

Cell Destruction ◽

Histocompatibility Complex ◽

Mhc Class I Molecules

The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.

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