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D S Latchman

Publications and source records attributed to D S Latchman.

At least 307 records · Page 17Linked to original sources
PubMed1990

Detection in non-erythroid cells of a factor with the binding characteristics of the erythroid cell transcription factor EF1.

The erythroid transcription factor erythroid factor-1 (EF1) plays a critical role in the transcription of erythroid-specific genes. Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of EF1 at low abundance in a wide variety of non-erythroid cell types. This is the first report of an EF1-like activity in non-erythroid cells and indicates that this factor may play a role in the regulation of genes expressed in such cells.

Animals↗
PubMed1990

Mononuclear phagocytes and HSV-1 infection: increased permissivity in differentiated U937 cells is mediated by post-transcriptional regulation of viral immediate-early gene expression.

Undifferentiated U937 cells are non-permissive for herpes simplex virus (HSV) infection but can be rendered permissive by treatment with phorbol myristate acetate (PMA), which causes them to differentiate to a macrophage-like phenotype. Following infection with HSV, both PMA--treated and untreated cells correctly transcribe the viral immediate-early genes at levels comparable to those observed in fully permissive cell types, but immediate-early RNA and protein are detected only in the PMA-treated cells. Hence PMA acts by relieving an early block to HSV infection caused by the rapid turnover of immediate-early RNA. This block is not caused by the production of soluble inhibitors and can also be relieved by treatment with other agents that cause macrophage differentiation such as 1, 25 dihydroxycholecalciferol. These findings therefore indicate that the non-permissivity of undifferentiated U937 cells for HSV is mediated by post-transcriptional regulation of immediate-early gene expression.

Cell Line↗
PubMed1990

Cell lines derived from dorsal root ganglion neurons are nonpermissive for HSV and express only the latency-associated transcript following infection.

The effect of herpes simplex virus type 1 infection in a series of immortalized dorsal root ganglion cell lines has been investigated. Following infection of one of these lines, the viral immediate-early genes are not transcribed and the lytic cycle is aborted at an early stage. In contrast these cells do support transcription of the gene encoding the latency-associated transcripts which are the only viral RNAs present in latently infected ganglia in vivo. These cell lines are therefore a suitable model system for studies of the processes regulating the interaction of HSV with neuronal cell types and the establishment of latent infections in vivo.

Animals↗
PubMed1990

Octamer motif mediates transcriptional repression of HSV immediate-early genes and octamer-containing cellular promoters in neuronal cells.

C1300 mouse neuroblastoma cells are nonpermissive for infection with herpes simplex virus owing to a failure of viral immediate-early gene transcription following infection. The weak activity of the immediate-early gene promoters in these cells is mediated by the binding of a repressor factor to the octamer-related TAATGARAT motifs in these promoters. This repressor activity is specific to cells of neuronal origin (being absent in a range of permissive nonneuronal cells) and is also able to repress the activity of cellular octamer-containing promoters introduced into C1300 cells. The role of this repressor in the regulation of octamer-containing cellular genes in neuronal cells and in the control of latent infections with herpes simplex virus is discussed.

Animals↗
PubMed1990

A repeated proline-rich sequence in Sm B/B' and N is a dominant epitope recognized by human and murine autoantibodies.

Reactivity of a murine monoclonal anti-Sm B antibody was localized to a cDNA clone T3/2 encompassing codons 177-221 of Sm N and to a series of 10-residue synthetic peptides containing a proline-rich motif. Human sera containing anti-B antibodies also bound to this proline-rich motif in the form of a heptamer, PPGMRPP, and could distinguish the N/B sequence from similar sequences present in the RNP A and C polypeptides in a number of cases. Monoclonal antibodies binding to either this peptide or to a determinant present on both B and D polypeptides inhibited the majority of anti-B binding in 50% of anti-B sera. The region of N/B containing PPGMRPP also bears a second epitope, sterically blocked by monoclonal antibody KSm 5. This hotspot binds 40-60% of anti-B activity in 30% of anti-B sera. These data suggest that the anti-Sm B epitope recognition repertoire is restricted in SLE patients.

Amino Acid Sequence↗
PubMed1990

Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript.

By using chloramphenicol acetyltransferase (CAT) assays in neuron-derived cell lines, we show here that promoter activity associated with the herpes simplex virus type 1 latency-associated transcript (LAT) had neuronal specificity. Promoter activity in these transient CAT assays coincided with a DNA region containing excellent RNA polymerase II promoter consensus sequences. Primer extension analysis in a LAT promoter-CAT plasmid construct placed the start of transcription about 28 nucleotides from the first T in the consensus TATA box sequence. Neuronal specificity of this promoter was suggested by examining the effect of sequences upstream of the promoter on CAT activity in neuronal versus nonneuronal cells. In nonneuronal cells, promoter activity was decreased 3- to 12-fold with the addition of upstream sequences. In contrast, in neuron-derived cells, the addition of upstream sequences did not decrease promoter activity. The LAT promoter predicted by our transient CAT assays was located over 660 nucleotides upstream from the 5' end of the previously mapped 2-kilobase (kb) LAT. This unusual location was explained by in situ and Northern (RNA) blot hybridization analyses that suggested that LAT transcription began near the promoter detected in our CAT assays, rather than near the 5' end of the 2-kb LAT. In situ hybridization with neurons from latently infected rabbits detected small amounts of LAT RNA within 30 nucleotides of the consensus TATA box sequence. This suggested that LAT transcription began near this TATA box. Northern blot hybridization of RNA from ganglia of latently infected rabbits revealed a faint 8.3-kb band of the same sense as LAT. We conclude that (i) the LAT promoter has neuronal specificity, (ii) the LAT promoter is located over 660 nucleotides upstream of the 5' end of the previously characterized stable 2-kb LAT, (iii) LAT transcription begins about 28 nucleotides from the first T of the consensus TATA box sequence and extends to near the first available polyadenylation site approximately 8.3 kb away, and (iv) this 8.3-kb RNA may be an unstable precursor of the more stable 2- and 1.3-kb LATs.

Animals↗
PubMed1990

Regulated expression of the small nuclear ribonucleoprotein particle protein SmN in embryonic stem cell differentiation.

The SmN protein is a component of small nuclear ribonucleoprotein particles and is closely related to the ubiquitous SmB and B' splicing proteins. It is expressed in a limited range of tissues and cell types, including several undifferentiated embryonal carcinoma cell lines and undifferentiated embryonic stem cells. The protein declines to undetectable levels when embryonal carcinoma or embryonic stem cells are induced to differentiate, producing primitive endoderm or parietal endoderm or yielding embryonal bodies. This decline is due to a corresponding decrease in the level of the SmN mRNA. The potential role of SmN in the regulation of alternative splicing in embryonic cell lines and early embryos is discussed.

Actins↗
PubMed1990

Inhibition of histone H2B gene transcription and of cellular growth by a truncated viral trans-activator protein.

The herpes simplex virus virion protein Vmw65 trans activates the viral immediate-early genes and some octamer-containing cellular genes, including that encoding histone H2B. We found, however, that a truncated form of this virion protein repressed H2B gene transcription and also dominantly inhibited induction of the gene by intact Vmw65. A cell line expressing this truncated protein expressed reduced levels of H2B and grew more slowly than the parental cell line or a similar line expressing the intact protein.

Animals↗
PubMed1990

Cell-type-specific splicing factors and the regulation of alternative RNA splicing.

A very wide variety of biological processes are regulated by alternative splicing. By this means, a gene can be transcribed in several different tissues but in each tissue the RNA transcript is spliced in a particular way to produce a different mRNA and hence a different protein. It is now clear that alternative splicing is regulated by factors which are expressed in a tissue-specific manner and which are necessary for the splicing events to occur. This review will discuss the evidence for the existence of these factors, their nature, and the mechanisms by which they regulate splicing by interacting with sequences in the RNA.

Animals↗
PubMed1989

HSV infection induces increased transcription of Alu repeated sequences by RNA polymerase III.

The Alu family of repeated sequences is transcribed by both RNA polymerase II and RNA polymerase III. In cells infected with HSV, transcription by polymerase III increases while transcription by polymerase II decreases. By using virus strains carrying mutations in the genes encoding individual regulatory proteins, we have shown that this effect is dependent upon the immediate-early protein ICP27 and occurs by a process distinct from those which regulate viral gene expression. This is the first example of increased transcription of endogenous cellular sequences by RNA polymerase III during infection with a DNA virus.

Cell Nucleus↗
PubMed1989

The different competitive abilities of viral TAATGARAT elements and cellular octamer motifs, mediate the induction of viral immediate-early genes and the repression of the histone H2B gene in herpes simplex virus infected cells.

An HSV virion component, Vmw65, interacts with cellular transcription factors to transactivate TAATGARAT-containing viral genes and some cellular genes containing the related octamer element. We show that the octamer-containing histone H2B promoter can be trans-activated by transfection of Vmw65 but not by viral infection. The induction of H2B transcription by Vmw65 can be abolished by co-transfection of excess amounts of either a TAATGARAT element or a Vmw65 responsive octamer element. This effect cannot be overcome by addition of increasing amounts of Vmw65. The H2B promoter and TAATGARAT-containing viral promoters therefore compete for limiting cellular factors required for induction by Vmw65 resulting in repression of the H2B gene during lytic infection. The competitive effect of TAATGARAT elements on the H2B gene is not observed in the absence of Vmw65, but can be produced in the presence of a truncated form of Vmw65 lacking the acidic tail required for transcriptional activation. Hence a domain of Vmw65 distinct from that involved in transcriptional induction interacts with cellular octamer binding proteins favouring binding to the TAATGARAT motif.

Base Sequence↗
PubMed1989

Isolation of cDNA clones encoding the human Sm B/B' auto-immune antigen and specifically reacting with human anti-Sm auto-immune sera.

A cDNA clone for the human SmB and B' auto-immune antigens has been isolated by antibody screening of a cDNA expression library. The cDNA clone hybridises with two distinct mRNAs, one of which is expressed in a tissue-specific manner. A fusion protein expressed from the cDNA clone was recognised by a number of sera from systemic lupus erythematosus (SLE) patients containing anti-Sm antibodies but not by sera reactive with other auto-immune antigens. The potential use of this clone in a diagnostic assay for SLE and in elucidating the processes regulating the expression of SmB and B' is discussed.

Amino Acid Sequence↗
PubMed1989

Expression of the SmB' splicing protein in rodent cells capable of following an alternative RNA splicing pathway.

The expression of the SmB and SmB' spliceosome proteins in a variety of cell types and tissues has been investigated. Although SmB is found in all cells studied, the SmB' protein is found only in a small number of rodent cell types. The presence of this protein is correlated with the ability to utilize an alternative pathway of RNA splicing which is not available in most cell types. This is the first demonstration of tissue specific expression of a protein component of the spliceo-some and suggests a role for SmB' in the regulation of some cases of alternative RNA splicing.

Animals↗
PubMed1989

Levels of the 90kd heat shock protein and resistance to glucocorticoid-mediated cell killing in a range of human and murine lymphocyte cell lines.

The 90kd heat shock protein is associated with the receptors for glucocorticoids and other steroids. The steroid is believed to function by releasing the receptor from hsp90 allowing the receptor to bind to DNA and activate transcription. The levels of hsp90 have been measured in a variety of lymphoid cell lines and compared with their sensitivity to steroid mediating killing. No correlation of high hsp90 levels with steroid resistance was observed. However, increased levels of hsp90 in response to steroid were observed in a number of cell lines. The significance of these findings is discussed in terms of the modulation of the cells response to steroid treatment and the mechanism of steroid resistance.

Animals↗
PubMed1989

The herpes simplex virus type 1 immediate-early protein ICP27 is obligately required for the accumulation of a cellular protein during viral infection.

Lytic infection with herpes virus type 1 (HSV-1) causes the accumulation of a 40-kDa cellular protein (p40) which is also overexpressed in cultured cells transformed by HSV or other agents and in human cervical tumors. Accumulation of p40 is dependent upon viral protein synthesis but not viral DNA replication in the infected cell and occurs in the HSV-1 mutants tsK and tsLB2 in which only a defective ICP4 protein and the four other immediate-early proteins are synthesized. By using a panel of HSV-1 strains, each defective in one of these four proteins, we show that only a mutation in the gene encoding ICP27 abolishes p40 accumulation. The defect in this mutant virus can be rescued by a plasmid encoding ICP27 alone indicating that ICP27 is obligately required for p40 accumulation. The significance of this effect as one aspect of the interaction of viral control proteins with cellular genes is discussed.

Animals↗
PubMed1989

Regulated transcription of herpes simplex virus immediate-early genes in neuroblastoma cells.

C1300 neuroblastoma cells are nonpermissive for infection with herpes simplex virus but can be rendered permissive by pretreatment with sodium butyrate. This increased permissivity which is specific for HSV is caused by increased transcription of the viral immediate-early genes following infection of butyrate-treated cells and can be observed for at least 24 hr following withdrawal of butyrate. The use of C1300 cells as a model system for studying the regulation of immediate-early gene expression in neuronal cells in vitro and its possible relevance to the study of the processes regulating latent infection in vivo is discussed.

Animals↗