PubMed Health⌕ Search

Biomedical subjects

D Mathis

Publications and source records attributed to D Mathis.

156 records · Page 9Linked to original sources
PubMed1987

Properties of a CCAAT box-binding protein.

NF-Y is a sequence-specific DNA-binding protein that interacts with the conserved Y motif of the major histocompatibility complex class II gene, E alpha. Since it is actually a CCAAT box-binding protein, NF-Y also attaches to other promoters bearing CCAAT sequences; yet, it is neither of the previously described transcription factors, CBP or CTF/NF-1. In this report, we document the cell-type distribution and various biochemical properties of NF-Y. The most important findings are that this protein is ubiquitously distributed, that it is probably a metallo-protein, that it has a protease-resistant DNA-binding domain and that the NF-Y/E alpha-olgo complex seems extremely large (greater than 200kD). These data should prove useful in comparisons of NF-Y with other sequence-specific DNA-binding proteins; they have already provided new insights into NF-Y's structure.

Animals↗
PubMed1987

A multiplicity of CCAAT box-binding proteins.

NF-Y is a sequence-specific DNA-binding protein that recognizes the Y box, a promoter element common to all major histocompatibility complex class II genes. Since the 14-base Y element harbors a CCAAT box in reverse, we were prompted to ask whether NF-Y is actually a CCAAT box-binding protein and whether it is related to the previously described CCAAT-binding factors CBP and CTF/NF-I. Data from gel retardation, methylation interference, saturation mutagenesis, and cross-competition experiments establish definitively that NF-Y is an entirely distinct CCAAT box-binding entity. Moreover, these experiments have uncovered a fourth CCAAT-binding protein, NF-Y(star) that interacts with the thymidine kinase promoter. Clearly, then, there exists a multiplicity of factors that recognize CCAAT sequences; it now becomes imperative to understand the functional significance of this multiplicity.

Animals↗
PubMed1987

Conserved major histocompatibility complex class II boxes--X and Y--are transcriptional control elements and specifically bind nuclear proteins.

A conserved sequence motif exists at the 5' end of all major histocompatibility complex class II genes. This motif consists of the 14-base X and Y boxes separated by a short stretch of variable sequence. In this report, we provide evidence that the X and Y boxes play an important role in controlling transcription of the murine class II gene E kappa alpha. We have developed transgenic mouse lines that carry E alpha genes cleanly deleted for either the X or Y box and have compared the expression of these mutant transgenes with that of a nondeleted control. Both the X and Y segments appear critical for accurate and efficient transcription of E kappa alpha. The most drastic effect is seen with gamma-interferon-treated macrophages, where deletion of the Y box completely abrogates transcription initiated by the normal promoter. In addition, we identify proteins from nuclear extracts that bind specifically to the X or Y box.

Animals↗
PubMed1986

Functional sites on Ia molecules: a molecular dissection of A alpha immunogenicity.

Ia antigens are polymorphic cell-surface molecules that control the immune response. We have begun to localize important functional sites on one of the Ia molecules, A alpha. Herein, we focus on the A alpha k and A alpha b alleles and ask what defines "b-ness" and "k-ness" for a panel of monoclonal antibodies. Two independent experimental strategies are employed: the ability of 12 monoclonal antibodies to recognize L cell transfectants bearing chimeric and mutant A alpha chains is assessed, and the amino acid sequences of A alpha chains expressed by immunoselected B lymphoma mutants are deduced. For each antibody, we identify a stretch of polymorphic residues critical for recognition; for several, we can pinpoint a single amino acid. Certain stretches of A alpha (depending on the allele) appear strikingly immunodominant.

Amino Acid Sequence↗
PubMed1986

E alpha u and E beta u chain association: where lies the anomaly?

H-2u haplotype mice are unique among all E alpha+ strains because they do not provide in heterozygotes an E alpha chain that interacts with E betak,s,etc. sufficiently well to allow certain E-restricted immune responses. As a first step in understanding this peculiarity, we have sequenced E alpha u and E beta u cDNA and compared the derived amino acid sequences with those of previously analyzed alleles. Although no glaring structural abnormalities were found, we have identified some u-specific residues and suggest which are the most likely to provoke a pairing anomaly.

Alleles↗
PubMed1986

Behavioral impairments related to cognitive dysfunction in the autoimmune New Zealand black mouse.

The possibility that autoimmunological disorders involving neuronal constituents as autoantigens can result in measurable behavioral impairments prompted the behavioral analysis of the New Zealand black (NZB) mouse strain, known to have high levels of brain-reactive antibodies. Sensorimotor competence and performance in tasks requiring learning and memory were assessed in 7-10-month-old NZB and contrasted with those of CFW mice. The NZB mice showed pronounced deficits in performance of passive and active shock avoidance responses. These deficits could not be accounted for by the slight sensorimotor disadvantage of NZB mice relative to CFW mice. No difference between the two mouse strains was seen in passive avoidance behavior at 1.5 months of age. It is concluded that NZB mice display a behavioral deficit related to cognitive dysfunction and that autoimmune mechanisms may be involved in the etiology of this deficit. Such behavioral disturbances produced by an autoimmune mechanism may have relevance for the neurological declines observed in aging, since the incidence of autoimmune disorders increases markedly in old age.

Animals↗
PubMed1986

Altered I-J phenotype in E alpha transgenic mice.

One of the more intriguing puzzles in immunology is the genetic basis for control of murine T-cell I-J determinants. Molecules bearing I-J determinants (I-J molecules) play a role in information trafficking among immunocompetent cells, probably serving as self-recognition molecules that channel regulatory factors to their appropriate target cells. Although it is clear that I-J polymorphism is influenced by the major histocompatibility complex (MHC), molecular genetic studies provide evidence that an MHC gene does not encode I-J molecules. A possible explanation for this paradox is that I-J molecules are a set of non-MHC-encoded T cell receptors that are directly or indirectly selected for by self-MHC products. One key to resolving the genetic and molecular basis for control of I-J determinants is the identification of the MHC gene(s) involved. Herein, data are presented which show that E alpha transgenic mice express an altered I-J phenotype, providing clear evidence that I region class II genes influence I-J polymorphism. Although further study is required to resolve how class II genes mediate this effect, this is a major piece to the I-J puzzle.

Animals↗
PubMed1985

A molecular basis for the Ia.2 and Ia.19 antigenic determinants.

The murine Ia antigens, heterodimeric glycoproteins on the surface of immunocompetent cells, restrict immune recognition by their influence on cell-cell interactions. Many serological specificities have been mapped to these molecules, and monoclonal antibodies directed against some of these determinants block antigen presentation to T lymphocytes. As a step toward a better understanding of Ia function, we sought to define the molecular basis of Ia.2 and Ia.19, specificities found on the A alpha chain of only the k or of both k and r haplotypes, respectively. We report nucleotide sequences for the A alpha chain cDNAs of the k, r, and s haplotypes, which, when compared to previously published A alpha sequences, demonstrate the existence of one k-specific amino acid residue and of another present only in the k and r haplotypes. These residues must thus play an important role in the generation of Ia.2 and Ia.19 specificities.

Alleles↗
PubMed1983

Properties of reticulum cell sarcomas in SJL/J mice. VIII. Prominent role of RCS cell I-A antigens in the stimulation of syngeneic T cells.

While T cells from SJL and from F1 hybrids of SJL that do not express I-E antigens give strong proliferative responses to RCS, T cells from F1 hybrids expressing surface I-E do not. The nature of the stimulating antigen on the RCS cell surface was examined using monoclonal antibodies. Complete inhibition of the T-cell proliferative response was obtained with antibodies to I-A antigens, whereas antibodies to I-E antigens did not inhibit at all. This inhibition was mediated via an effect of the antibodies on the stimulating cells. Biochemical characterization of immunoprecipitated 125I-and 35S-labeled RCS antigens was performed using two-dimensional gel electrophoresis. Using this technique, I-A antigens were readily detected. However, neither Ia.7-specific antibodies nor antibodies specific for E alpha: E beta complexes precipitated any E alpha or E beta chains. Comparison of I-A antigens from RCS and normal SJL spleen cells revealed minor mobility differences in the gels, possibly due to differences in glycosylation, the significance of which needs to be further evaluated. Examination of RNA extracted from RCS, using E alpha and A alpha cDNA probes showed that RCS cells do not transcribe the E alpha gene as has been shown previously for normal H-2s cells. Furthermore, DNA from RCS cells showed a defect in the E alpha gene similar to that known to exist in normal H-2s cells. Our findings exclude the presence of E alpha on RCS cells and suggest a major role for I-A, either alone or in conjunction with another as yet unidentified cell surface antigen, in the stimulation of T cells.

Animals↗
PubMed1980

Transcription units of chicken ovalbumin gene observed after injection of cloned complete genes into Xenopus oocyte nuclei.

The organization of transcription of a well-characterized protein encoding gene was studied by microinjection and electron microscopy. Circular recombinant DNA molecules containing the complete chicken ovalbumin sequences (7.7 kilobases, contained in 11.5 kilobases of chicken DNA) were microinjected into germinal vesicles of living oocytes of the clawed toad Xenopus laevis, and their transcription was studied in nuclear spread preparations. Evaluation of spread chromatin showed a limited number of observed molecules transcribed in "specific" patterns--i.e., circular chromatin molecules containing transcription units approximately 2.3 micrometer long, consisting of regular series of densely packed lateral ribonucleoprotein fibrils gradually increasing in length. The appearance of these fibril gradients was similar to that of actively transcribed endogenous protein encoding genes contained in lampbrush-chromosome loops of the same nuclei and to the putative Bombyx silk fibroin transcription units. In addition, less-regular arrays of transcript fibrils were seen in some circles, including fully fibril-covered molecules, indicative of the occurrence of irregular transcriptional events. The results of this heterologous transcription experiment indicate that the transcriptional machinery of the amphibian oocyte nucleus is capable of transcribing protein encoding genes from an avian species in typical regular arrays of transcription units.

Animals↗
PubMedDate not supplied

Correcting an immune-response deficiency by creating E alpha gene transgenic mice.

We have introduced a cloned Ek alpha gene into embryos of mice incapable of expressing their endogenous E alpha genes. The transcription of Ek alpha was accurate and tissue-specific in the resulting transgenic lines and, in macrophages, Ek alpha transcription could be induced by gamma-interferon. The injected gene conferred on the genetically deficient host strain the ability to mount an immune response to a synthetic polymer.

Animals↗