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M Fellous

Publications and source records attributed to M Fellous.

At least 127 records · Page 7Linked to original sources

The protein encoded by a murine male germ cell-specific transcript is a putative ATP-dependent RNA helicase.

The murine PL10 cDNA corresponds to a transcript expressed only in the male germ line. Its expression is developmentally regulated, with high levels of transcripts being present during the meiotic and haploid stages of spermatogenesis. The deduced protein is shown to be highly homologous to the murine translation initiation factor eIF-4A and to other proteins that are also homologous to eIF-4A, including the Drosophila protein vasa. By consensus sequence conservation and comparison of secondary structure predictions, putative mononucleotide binding and DNA/RNA binding domains are proposed to be shared by all these proteins. Taken together, these results suggest a helicase function for PL10 protein similar to that of eIF-4A and suggests its possible role in a key step of the spermatogenic process. The possible significance of the similarity between the PL10 protein and the protein product of the maternal effect gene vasa is also discussed.

Amino Acid Sequence↗

Characterization of human IFN-gamma response using somatic cell hybrids of hematopoietic and nonhematopoietic origin.

A panel of 27 rodent-human somatic cell hybrids composed of cells of hematopoietic (nonadherent cells) and nonhematopoietic origin (adherent cells) was used to identify the chromosomes involved in the biological response to human IFN-gamma (Hu-IFN-gamma). We found that the stimulation of class-I histocompatibility antigen expression correlates with the presence of human chromosomes 6 and 21 in adherent cell hybrids, while human chromosome 6 alone is sufficient in nonadherent hybrids. Scatchard analysis of the binding of radiolabeled Hu-IFN-gamma to nonadherent cell hybrids gave a Kd value similar to that found on human cell lines. Induction of a reporter gene placed under the transcriptional control of the interferon responsive sequence (IRS) in adherent cell hybrids requires both chromosomes 6 and 21. The antiviral protection by Hu-IFN-gamma in adherent cell hybrids was reached at physiological doses (2 units/ml) when human chromosomes 6 and 21 were present, while higher doses of Hu-IFN-gamma (5000 units/ml) were required for hybrids lacking chromosome 21. Thus, we demonstrate that differences exit in the response to Hu-IFN-gamma depending on the origin of the cell type.

Animals↗

Regulation of HLA-DR gene by IFN-gamma. Transcriptional and post-transcriptional control.

IFN-gamma increases the synthesis and level of mRNA of the HLA class I and II genes, in human cells such as melanomas which normally express both classes of molecules. It also induces the surface expression and mRNA synthesis of HLA-DR genes on cells which normally do not express HLA class II genes such as skin fibroblasts. We have investigated the mechanism by which IFN-gamma increases mRNA levels for class II MHC antigens in human cells. For this purpose, we have studied the effect of IFN-gamma on HLA-DR-alpha transcription rate in two different human cell types: VAL melanoma and JDA2 skin fibroblasts. HLA-DR-alpha mRNA is spontaneously produced in VAL cells and its level is enhanced upon IFN-gamma treatment. We demonstrate here that IFN-gamma increases the transcription of HLA-DR-alpha gene in this cell line. However, the discrepancy observed between HLA-DR-alpha mRNA and transcriptional rates led us to postulate that IFN-gamma also regulates the HLA-DR-alpha gene post-transcriptionally. In the course of these experiments, we found also that human skin fibroblasts, which do not contain detectable amounts of HLA-DR-alpha mRNA, spontaneously transcribe the HLA-DR-alpha gene.

Cell Line↗

Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe.

Chromosome preparations from seven subjects with aberrations of sex chromosomes were utilized for in situ hybridization studies with the tritium-labeled Y-derived probe p50f. Two subjects had a pseudodicentric chromosome consisting of two copies of Yp and a portion of Y long arm; two were XX males [46,XX,t(Xp;Yp)], one was missing part of the Y short arm, and another had t(5p;Yq); in addition cells from an XYY male as well as a normal 46,XY male, and a 46,XX female, were hybridized with the same probe. The hybridization technique of Harper and Saunders (1981) was used. There was excess labeling of the Yp/paracentromeric regions in the cases with the normal Y, the XYY, the pseudodicentric Y, and the 5/Y translocation. No significant label was seen on metaphases from the normal 46,XX female or the female with the partially missing Y short arm. Excess label was present on the X short arm in the cases of the XX males; there were 8% and 9.5% of cells with label. The combined cytogenetic and hybridization data indicate that one X short arm in these XX males has undergone a translocation with Yp, and that genes for sex determination probably reside on the distal half of the Y short arm.

Chromosome Banding↗

Testis-specific transcripts detected by a human Y-DNA-derived probe.

A genomic sequence (12f3), derived from the long arm of the human Y chromosome, detects a 1.6 kb mRNA, expressed in human and mouse testis, but not in other tissues tested by Northern blot analysis. Using 12f3 as a probe, a mouse cDNA, designated PL5, was isolated from an adult mouse testis cDNA library. The profile obtained by Southern blot analysis using PL5 as probe under high-stringency conditions, reveals that 12f3 probably represents a Y-located pseudogene which was derived from an autosomally located gene. Southern blot analysis of different vertebrate species, using probe PL5, shows that this gene has been highly conserved during evolution. Preliminary in situ hybridizations on testis tissue sections indicate that PL5 is expressed during the postmeiotic stages of male germ cell differentiation and thus may play a role during spermatogenesis. A second cDNA, also obtained from the testis cDNA library, weakly cross-reacts with 12f3. This cDNA, designated PL10, detects a mRNA of approximately 4 kb which is highly expressed in mouse testis, but not in male or female mouse liver. The gene corresponding to this cDNA is also well conserved among vertebrates.

Chromosome Mapping↗

The p12f2/TaqI Y-specific polymorphism in three groups of Italians and in a sample of Senegalese.

The TaqI/p12f2 Y-specific RFLP was studied in 258 Italians (69 from North, 74 from Centre-South and 115 from Southern Sardinia) and in 65 Senegalese. The two allelic fragments of 10 and 8 kb characterizing this polymorphism were both found in the Italians but only the 10 kb band was found among the Senegalese. The observed frequency of the 8 kb allele was 32.4% in Central-Southern Italians, 17.4% in Northern Italians and 13.0% in Southern Sardinians. The last figure is significantly lower than that (34.3%) previously reported for a smaller sample of the same population.

Alleles↗

[An XX male newborn infant. A genetic and endocrinologic study].

The second child of a non consanguineous couple had a male phenotype with two intrascrotal testes of normal size however a scrotum bifidum was noted. The karyotype of the child was 46 XX and the parents one's was normal. No Y specific sequence was detected by using four Y specific probes (47 B, 12 F3, 52 D and 118). During the first semester of life, hormonal investigations showed a normal testicular function.

Androgens↗

[XX male syndrome: a study model of the genetic determination of the male sex].

Using Y-specific probes, issued from a library of the human Y chromosome, DNA from about 30 XX men has been studied by the Southern technique. Two groups of patients could be distinguished: one with Y genetic material, the second, without Y DNA. Among XX males with Y sequences there was a genetic heterogeneity with a variable amount of Y DNA sequences. These Y DNA sequences come from the short arm of the Y chromosome and are probably translocated to the paternal X. Concerning the other group, in which no Y sequence could be detected, either Y DNA was present but was not detected, or the mechanism of maleness was Y-independent.

Base Sequence↗

Small deletions of the short arm of the Y chromosome in 46,XY females.

Structural anomalies of the sex chromosomes provide a means to study the location of genes responsible for sex determination. Recently, a type of sex reversal in humans, the 46,XX male, was shown to result in some cases from translocation of Y chromosome material to the X chromosome. In the present report, another type of sex reversal, the 46,XY female, is shown to result, in two cases, from small deletions of the short arm of the Y chromosome. Prometaphase chromosome analysis showed a 46,X,Yp- karyotype. Several Y chromosome-specific DNA probes were found to be deleted in the two female patients. DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination.

Chromosome Deletion↗

A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance.

A human DNA sequence (p12f2), derived from a partial Y-chromosome genomic library and showing homology with the X and Y chromosomes and with an undetermined number of autosomes, detected two Y-specific restriction fragment length variants on male DNA that had been digested with Taq I and Eco RI. These variants may have been generated through a deletion-insertion mechanism and their pattern of holoandric transmission indicates that they represent a two-allele Y-linked polymorphism (RFLP). By means of DNA from patients with inborn deletions in chromosome Y, this polymorphic DNA site was mapped to the interval Yq11.1-Yq11.22. The frequency of the rarest allele was about 35 percent in Algerian and Sardinian human males, whereas it was only 4 percent among Northern Europeans. The p12f2 probe also detected Y-specific DNA fragments in the gorilla and chimpanzee. In view of the monosomy of the Y chromosome in mammalian species, Y-linked RFLP's may prove to be more useful than autosomal or X-linked markers in estimating genetic distances within and between species.

Base Sequence↗

Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate.

Using sodium butyrate and alpha, beta, and gamma interferons as inducing agents it has been possible to demonstrate the triggering of HLA class I antigen synthesis in the K562 cell line. This cell line, widely used to study hemopoietic differentiation, does not naturally express HLA antigens. This effect was confirmed by the detection of HLA class I antigens on the cell membrane with specific monoclonal antibodies, by immuneprecipitation, and by isolation of specific HLA ABC messenger RNA, in the induced cells. No synthesis of HLA class II antigens was observed. Because leukemic cells can be considered as a model representing certain stages of normal hemopoietic differentiation, the expression of HLA antigens on K562 cells induced to differentiate could be interpreted as an event related to the process of differentiation itself. The lack of expression of DR antigens may result from a genetic defect as observed for beta 2-microglobin in Daudi cells.

Antibodies, Monoclonal↗