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Biomedical subjects

I Bach

Publications and source records attributed to I Bach.

At least 37 records · Page 2Linked to original sources
PubMed1992

An autosomal homologue of the choroideremia gene colocalizes with the Usher syndrome type II locus on the distal part of chromosome 1q.

Employing the mouse homologue of the human choroideremia cDNA as a probe, we have identified a homologous human gene. The consensus cDNA of this gene, designated human choroideremia-like (hCHML) gene, encompasses an open reading frame of 1968 base pairs. The deduced polypeptide of hCHML displays several regions of homology to smg p25A GDI, a bovine protein known to regulate the GDP/GTP exchange of the GTP-binding protein smg p25A. hCHML is located at 1q31-qter, a chromosomal region which, by means of linkage analysis, was previously shown to carry a gene locus for Usher syndrome type II. The colocalization of hCHML and Usher syndrome type II, as well as the clinical similarities between choroideremia and Usher syndrome type II, make hCHML a candidate gene for this disorder.

Amino Acid Sequence↗
PubMed1992

Microdeletions in patients with gusher-associated, X-linked mixed deafness (DFN3).

Employing various probes from the proximal part of the Xq21 region, which is known to harbor the DFN3 gene, we have investigated 13 unrelated male probands with X-linked deafness, to detect possible deletions. For two of these patients, microdeletions could be detected by using probe pHU16 (DXS26). One of these deletions also encompasses locus DXS169, indicating that it extends farther toward the centromere. The presence of normal hybridization patterns in the DNA of 25 unrelated control males suggests that these deletions are the primary cause of progressive mixed deafness in these patients. If so, their molecular characterization may pave the way for the identification and isolation of the corresponding gene.

Chromosome Deletion↗
PubMed1991

Two members of an HNF1 homeoprotein family are expressed in human liver.

HNF1 is a transcriptional activator, required for the liver-specific expression of a variety of genes, that binds to DNA as a dimer via the most diverged homeodomain known so far. We were interested to examine whether HNF1 is a unique homeoprotein example or whether it is the prototype of a new subfamily of homeodomain containing proteins. In this work we describe the isolation of a cDNA clone from a human liver library encoding a protein, highly homologous to HNF1 in three regions, including the homeo- and dimerization domains. We show that this protein can heterodimerize with human HNF1 in vitro. Sequence comparison of our clone with a rat variant HNF1 (vHNF1) clone, isolated in parallel in our laboratory from the dedifferentiated H5 hepatoma cell line, identified our cDNA as human vHNF1. vHNF1 is a nuclear protein recognizing the same binding site as HNF1 and previously thought to occur only in dedifferentiated hepatoma cells that fail to express most liver specific genes. Nevertheless, we show by Northern blot analysis that vHNF1 transcripts are present in differentiated human HepG2 hepatoma cells as well as in rat liver and that this transcript level is 10-20 fold lower than that of HNF1. We assigned the vHNF-1 gene to human chromosome 17 and murine chromosome 11. These chromosomal localizations differ from that of the HNF-1 gene indicating that both genes are not clustered on the genome.

Amino Acid Sequence↗
PubMed1990

A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain.

Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes. We report here the purification of this rat liver nuclear protein and the cloning of its cDNA using a PCR-derived approach. Seven independent clones reveal 3 alternative polyadenylation sites and a unique open reading frame. Both a motif homologous to the homeodomain and a distal dimerization domain are required for specific DNA binding. Sequence comparisons reveal several atypical features at key positions in the segment corresponding to helices III and IV of the Antaennapedia homeodomain as well as a potential 24 amino acid loop in place of the universal turn between helices II and III. Together with its property to dimerize in the presence or absence of DNA, these features place HNF1 as the prototype of a novel subclass of transcription factors distantly related to homeoproteins.

Amino Acid Sequence↗
PubMed1990

Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse.

HNF1 is a transcription factor that is required for hepatocyte-specific expression of several genes, including albumin and fibrinogen. Rat HNF1-encoding cDNAs have recently been cloned, revealing that this factor is a distant member of the homeoprotein family. We have now isolated HNF1 clones from a human liver cDNA library by using a rat HNF1 cDNA-derived probe. The longest clone, HCL20, contains a sequence corresponding to the intact rat HNF1-coding region followed by a 3' nontranslated region and a poly(A) tail, hence representing an almost full-length HNF1 cDNA. Alignment of the human and rat sequences shows that HNF1 is highly conserved between the two species. The HNF1 gene was mapped by in situ hybridization and by RFLP analysis of interspecific mouse backcrosses to chromosomes 12q24.3 and 5F in human and mouse, respectively, establishing a new segmental homology between these two chromosomes.

Albumins↗
PubMed1990

Anatomy of the rat albumin promoter.

The sequences preceding the albumin mRNA start site are able to direct efficient transcription only upon introduction into cells expressing the endogenous albumin gene. In transient expression assays, the activity of a reporter gene (CAT) linked to this promoter is 100-fold higher in H4II differentiated hepatoma cells than in H5 dedifferentiated cells which no longer express their albumin gene. This tissue specificity depends on the very proximal promoter region, composed of a CCAAT box, the proximal element and a TATA box. Deletion of the CCAAT box leads to a two- to threefold decrease in activity, deletion of the proximal element (PE) results in loss of activity. The PE is a high-affinity binding site for HNF1/APF, a strictly liver specific trans-acting factor. When the affinity of this factor for PE is decreased by bacterial methylation (PE includes a dam methylase site), by mutation, or by its replacement with the homologous element from the alpha-fetoprotein gene (AFP), the activity of the short promoter (PE plus the TATA box) is abolished. This activity can be rescued in the presence of the more upstream elements: DEII, DEI and the CCAAT box (recognized, respectively, by the NF1/CTF, C/EBP and NFY/ACF factors) which are then absolutely required. Our results suggest that the upstream elements contribute to promoter activity by stabilizing the HNF1-PE complex and not by direct interaction with TFIID or the RNA polymerase. It is probable that these elements, essentially dispensable in already differentiated hepatoma cells, play a crucial role during development or differentiation to activate the promoter in cells that contain a low concentration of HNF1 and/or an HNF1 unable to open inactive chromatin alone.

Animals↗
PubMed1989

The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation.

We have characterized in the accompanying paper (P. Herbomel, A. Rollier, F. Tronche, M.-O. Ott, M. Yaniv, and M. C. Weiss, Mol. Cell. Biol. 9:4750-4758, 1989) six different elements in the albumin promoter. One of them, the proximal element (PE), is the binding site for a strictly liver specific factor, APF/HNF1. This binding site contains a bacterial DAM DNA methylase methylation target sequence which, when methylated, decreases the affinity of the protein for this element. When the different albumin promoter constructions were prepared in an Escherichia coli deoxyadenosine methylase-negative strain, the respective contributions of the elements to the overall promoter activity were strikingly different. An intact proximal element plus the TATA box gave almost full transcriptional activity in transient transfection experiments and only in differentiated hepatoma cells of line H4II, whereas the distal elements (distal element III [DEIII], the NF1-binding site DEII, and the E/CBP-binding site DEI) had become essentially dispensable. Mutations affecting the CCAAT box showed only a two- to threefold decrease. When PE was methylated, mutated, or replaced by the homologous element from the alpha-fetoprotein gene, activity in the context of the short promoter (PE plus the TATA box) was abolished. However, activity was restored in the presence of the upstream elements, showing that cooperation with factors binding to the CCAAT box and distal elements favors the functional interaction of the liver-specific APF/HNF1 factor with lower-affinity binding sites.

Albumins↗
PubMed1989

[Carl Wunibalt Otto--communist, pharmacist and chemist].

Along with the cigarette factory worker P. Röser, the tailors P. J. Nothjung und F. Lessner, the editor H. Bürgers, the publisher H. Becker, the clerk J. Ehrhardt and the doctors R. Daniels, J. Klein, A. Jacobi and W. Reiff, the 1852 Cologne communist trial also tried the pharmacist and chemist C. W. Otto. His life and his work for the German revolutionary worker's movement in the ninetieth century, up till now hardy mentioned, is discussed with the aid of archive sources.

Chemistry↗