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F Claessens

Publications and source records attributed to F Claessens.

45 records · Page 3Linked to original sources
PubMed1990

Sequence-specific binding of androgen-receptor complexes to prostatic binding protein genes.

Prostatic binding protein is a complex glycoprotein comprising three components, C1, C2 and C3, organized into two different heterodimers (C1-C3 and C2-C3). The rat ventral prostate genes encoding all three constituent polypeptides are expressed under androgenic control. Analysis of genomic fragments containing the genes and flanking sequences revealed in each case one androgen receptor-binding region upstream of or within the promoter and another in the first intron. The effect of androgens on the expression of these genes may, therefore, be mediated by these direct receptor-DNA interactions. The genomic fragments which contain androgen receptor-binding regions all contain nucleotide sequences reminiscent of glucocorticoid response elements (GRE). Mutations in these sequences in restriction fragments and in synthetic oligonucleotides significantly decreased their affinity for androgen-receptor complexes and their introduction into nonspecific sequences conferred affinity for androgen-receptor complexes. Based on these data, a consensus sequence for putative androgen response elements (ARE) is proposed. However, despite the specific recognition of these sequences by the androgen receptor in vitro, only the C3(1) intronic fragment could confer significant androgen responsiveness on a heterologous promoter. While this could be due to the fact that the GRE-like sequences present in the other fragments are not strong AREs, alternative hypotheses are being investigated currently. Not least of these is that the similar localization of the binding sites in each gene might underlie a more complex androgen regulation mechanism.

Androgen-Binding Protein↗
PubMed1989

Functional characterization of an androgen response element in the first intron of the C3(1) gene of prostatic binding protein.

We demonstrate that the 204 bp intronic gene fragment of C3(1), which has a specific in vitro affinity for the androgen receptor, is able to confer androgen responsiveness to a heterologous promoter. This characteristic is completely destroyed by a single G----T substitution, affecting a 5'-TGTTCT-3' element that closely resembles the consensus sequence of the glucocorticoid and progesterone response elements (GRE/PRE). In fact we could show that this androgen response element (ARE) also acts as a similarly weak GRE or PRE in T-47D cells.

Androgen-Binding Protein↗
PubMed1989

The androgen-dependent rat prostatic binding protein: comparison of the sequences in the 5' part and upstream region of the C1 and C2 genes and analysis of their transcripts.

The complete gene encoding the polypeptide C1 of the complex androgen-controlled prostatic binding protein was isolated from a rat genomic library. A new genomic fragment (C2B) containing only the 5' part of a C2-related gene was also purified. The segments containing exon 1 and a large part of the adjacent sequences were analysed and compared with the corresponding region of the C2A gene which has been completely sequenced previously. The high structural similarity extending over a large part of all three genomic fragments suggests the duplication of a common ancestral gene, followed by a more recent duplication of the C2-coding region. However, since the structural similarity upstream of position -150 between C2A and C2B abruptly disappears and no transcripts specific for the C2B region can be detected in prostate RNA, we propose that at a later stage in evolution the C2B region was disrupted and inactivated. Despite the common origin and the similar regulation of the two active genes, C1 and C2A, the only obvious conserved structural element is the homopurine stretch located at position -400, although sequence motifs resembling steroid hormone response elements are present at several locations.

Androgen-Binding Protein↗
PubMed1988

A single 12.5-kilobase androgen-regulated mRNA encoding multiple proline-rich polypeptides in the ventral prostate of the rat.

Synthetic 32P-labeled oligonucleotides have been used to identify the prostatic proline-rich polypeptide (PRP) mRNA which has partially been characterized. The 14-mer d(G-G-T-T-C-T-G-C-A-T-A-A-T-G) complementary to the coding sequence for His-Tyr-Ala-Glu-Pro, a sequence element occurring in all 38-residue PRP variants, hybridizes specifically with a 12.5-kilobase mRNA which is clearly androgen-controlled. This oligonucleotide was used as an efficient primer for the construction of a PRP-specific lambda gt10 cDNA library. The nucleotide sequence of the inserts from several recombinant clones has been determined. This structural analysis revealed a PRP mRNA encoding a large precursor containing a number of tandemly repeated units. Each repeat codes for a sequence of 100 amino acids in which the highly conserved PRP sequence is embedded. From this polyprotein the large number of PRP variants must be generated by a post-translational processing mechanism which is still unknown. The high degree of conservation of both nucleotide and amino acid sequence in the entire unit also indicates that the PRP gene(s) likely evolved by multiplication of a 300-base pair ancestral DNA sequence. This has resulted in a noninterrupted repetitive DNA coding segment which is detected at the genomic level.

Amino Acid Sequence↗
PubMed1987

Rat prostatic binding protein: the complete sequence of the C2 gene and its flanking regions.

The complete sequence (2879 bp) of the androgen-controlled rat prostatic binding protein C2 gene and 1023 bp of the 5'- and 2127 bp of the 3'-flanking regions have been determined. The gene contains three exons (93, 203 and 147 bp) and two introns (1630 and 806 bp). It is flanked by two homopurine-homopyrimidine stretches of 55 and 131 nucleotides respectively, located at positions -405 and 4151. These sequences are remarkably sensitive towards S1-nuclease, indicating an altered DNA conformation under superhelical stress. Several palindromes and dyad structures are observed in the 5'-upstream region of the gene and at position -457, and 80% homology to the consensus sequence of a glucocorticoid receptor binding site is found.

Amino Acid Sequence↗
PubMedDate not supplied

Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation.

Steroid hormones control many physiological processes by activating specific receptors that act as transcription factors. In vivo, each of these receptors has a specific set of target genes, but in vitro the glucocorticoid, progesterone, mineralocorticoid and androgen receptors (class I receptors) all recognise response elements which are organised as inverted repeats of 5'-TGTTCT-3'-like sequences with a three nucleotide spacer. This poses the question how the in vivo specificity of the different steroid responses is mediated. To unravel the mechanisms involved, we have compared the structural features of the androgen-selective enhancers of the probasin, the secretory component and the sex-limited protein genes with those of non-selective enhancers in the mouse mammary tumour viral promoter and the C3(1) gene. The probasin promoter contains an androgen response element which is recognised with high affinity by the androgen receptor, but not by the other class I receptors. Swapping experiments between the DNA-binding domains of the androgen and glucocorticoid receptor revealed that it is not the first zinc finger, but rather the second zinc finger and part of the hinge region which contribute to this specificity. Three AR-specific aminoacids are involved in the probasin ARE recognition, but not in the C3(1) ARE binding by the AR. The location of these residues strongly suggests that an alternative dimerisation interface is involved in the probasin ARE binding. We could subsequently demonstrate that the AR binds direct repeats of 5'-TGTTCT-3'-like sequences in gel retardation assays as well as in transfection experiments. Moreover, the androgen-specific enhancers all contain direct repeats, and point mutations that change the nature of these elements into inverted repeats result in a change of specificity. It seems, therefore, that direct repeat elements can be the determinants of the AR-specificity. It will be exciting to learn how such DNA elements will affect the properties of the receptor dimer with respect to ligand binding, interactions between the aminoterminal domain and the ligand-binding domain, the recruitement of co-activators and cooperativity with other transcription factors.

Animals↗
PubMedDate not supplied

Treatment of two cases of perigraft seroma with fistulization to the skin.

Perigraft seromas are an uncommon complication of prosthetic vascular reconstructive surgery. The unclear etiology is perhaps partly responsible for a delay in diagnosis. Two cases with fistulization to the skin after implantation of a Dacron graft are presented. Relation to the graft material was observed in the first patient where successive identical graft implants caused each time recurrence of symptoms. In both patients the condition was successfully treated only after removal of the affected graft and replacement with a polytetrafluoroethylene prosthesis.

Aged↗