Proteins interacting with an androgen-responsive unit in the C3(1) gene intron

Celis, Linda; Claessens, Frank; Peeters, Benjamin; Heyns, Walter; Verhoeven, Guido; Rombauts, Wilfried

doi:10.1016/0303-7207(93)90165-g

Cited by 46 publications

(25 citation statements)

References 42 publications

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“…Using DNaseI hypersensitivity assay, which detects sites of altered chromatin structure that correlate with transcriptional regulation, Enerbäck et al [25] identified two enhancer regions present in introns 8 or 9 and in the 3' UTR of the LPL gene, which counteracted the negative effect of the −4 kb to −827 construct. The identification of regulatory elements in the LPL intronic regions is analogous to that described for several other genes which harbor regulatory elements in their introns [30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 79%

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

et al. 2008

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Lipoprotein Lipase (LPL) plays a pivotal role in lipid metabolism by hydrolyzing triglyceride (TG) rich lipoprotein particles. Abnormalities in normal LPL function are associated with the risk of coronary artery disease (CAD). A number of genetic variants have been identified in the LPL gene that affects different functions of the LPL protein. A common HindIII polymorphism in intron 8 (T/ G) of the LPL gene has been found to be associated with altered plasma TG and HDL-cholesterol, and CAD risk in several studies, but its functional significance is unknown. It has been shown that certain intronic sequence contain regulatory elements that are important for transcription and translational regulation of a gene. In this study we tested the hypothesis that this polymorphism affects the binding site of a transcription factor that regulates the transcription of LPL gene. Electrophoretic mobility shift assays revealed that the HindIII site binds to a transcription factor and that the mutant allele has lower binding affinity than the wild type allele. Transcription assays containing the entire intron 8 sequence along with full-length human LPL promoter were carried out in COS-1 and human vascular smooth muscle cells. The mutant allele was associated with significantly decreased luciferase expression level compared to the wild type allele in both the muscle (3.394 ± 0.022 vs. 4.184 ± 0.028; P=4.7 × 10 −6 ) and COS-1 (11.603 ± 0.409 vs. 14.373 ± 1.096; P<0.0001) cells. In conclusion, this study demonstrates for the first time that the polymorphic HindIII site in the LPL gene is functional because it affects the binding of a transcription factor and it also has an impact on LPL expression.

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Section: Discussionmentioning

confidence: 79%

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

et al. 2008

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“…3100) while a sequence at nt. 2243 (AGTtCGgagTGTTCT) is similar to a functional androgen response element in the rPSC3(I) gene (Celis et al, 1993). Two pairs of purine-rich repeats (`A' and`B' in Figure 5) at nucleotides 7668, 7199 and 7216, 7166 contains a polyoma enhancer-related (PEA3) motif, AGGAAG.…”

Section: Genomic Analysis Of Human Breast Tumorsmentioning

confidence: 99%

Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to Chromosome 11q13

et al. 1998

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The mammaglobin gene encodes a novel secreted protein whose corresponding mRNA is frequently up-regulated in human breast cancer. In non-malignant tissues, expression is also strictly limited to the mammary epithelium. To better understand the mechanisms controlling these patterns of expression, we have isolated the human mammaglobin gene and performed an initial assessment of its promoter activity. Mammaglobin gene architecture is very similar to that of a family of related genes that includes uteroglobin and rat prostatein subunits C1, C2, and C3. However, the mammaglobin gene itself is not well conserved phylogenetically. The human mammaglobin gene is localized by¯uorescent in situ hybridization to chromosome 11 band q13, a genomic region frequently ampli®ed in breast neoplasia. The sequence of proximal 1 kb of mammaglobin promoter contains several potential transcriptional control elements and directs high-level expression of a transfected reporter construct in human breast tumor cell lines. However, comparable levels of reporter gene expression are also seen in non-mammary human cell lines. These data suggest that, unlike related gene family members, the striking breast-speci®c expression and tumor-associated overexpression of mammaglobin is mediated by complex transcriptional control at more distal sequence elements.

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“…Transient transfections were done as described (14). Oligonucleotides (Table II) were cloned as dimers in the SalI site of a pBLCAT2-derived vector.…”

Section: Methodsmentioning

confidence: 99%

The Androgen-specific Probasin Response Element 2 Interacts Differentially with Androgen and Glucocorticoid Receptors

Claessens

Alen

Devos

et al. 1996

Journal of Biological Chemistry

134

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The nuclear receptors constitute a large family of transcription factors characterized by a well conserved DNA-binding domain. The receptors for glucocorticoids, progestins, mineralocorticoids, and androgens constitute a subgroup because they bind in vitro with high affinity to DNA elements containing a partial palindrome of the core sequence 5-TGTTCT-3. In vivo, however, the corresponding steroids differentially regulate the expression of their target genes, even when more than one receptor type is present in a particular cell.The DNA-binding domains of the androgen and of the glucocorticoid receptors bind most androgen response elements with similar relative affinities. In contrast, one element (5-GGTTCTTGGAGTACT-3) which was recently described in the promoter region of the probasin gene selectively interacts with the DNA-binding domain of the androgen receptor and not with that of the glucocorticoid receptor. From studies with chimeric elements, it can be deduced that it is the left subsequence 5-GGTTCT-3 which excludes the glucocorticoid receptor domain from binding.In co-transfection experiments where the ARE of the C3(1) gene is responsive to both androgens and glucocorticoids, the probasin element is induced only by androgens and not by glucocorticoids. The existence of response elements which are recognized preferentially by the androgen receptor provides yet another possible mechanism to explain the differences of the in vivo effects between androgens and other steroids of the subgroup.Nuclear receptors are transcription factors which mediate signals of a variety of hormones. Upon ligand binding, the receptors activate transcription by interacting with specific DNA sequences located within or near gene promoters.All members of the nuclear receptor superfamily bind with high affinity to directly or inversely repeated DNA sequences (1) by the DNA-binding domain (DBD) 1 which contains two zinc-finger motifs. Mader et al. (2) have demonstrated that differences between the glucocorticoid receptor (GR) and the estrogen receptor (ER) involving three amino acids located in the so-called P-box, are responsible for the difference in sequence recognition. The GR recognizes the sequence 5Ј-TGT-TCT-3Ј, while the ER interacts with the

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Proteins interacting with an androgen-responsive unit in the C3(1) gene intron

Cited by 46 publications

References 42 publications

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to Chromosome 11q13

The Androgen-specific Probasin Response Element 2 Interacts Differentially with Androgen and Glucocorticoid Receptors

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