Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.1 (S1 nuclease)
3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the sequence of 2770 nucleotides of 5' flanking sequence of the human estrogen receptor (hER) gene. The positions of potential binding sites for a number of trans-acting factors including Sp1, OTF-1, INR, TATA and CAAT box factors as well as several half palindromic hormone responsive elements (HREs) have been mapped by comparison with the consensus binding sequences. A long alternating purine/pyrimidine (APP) tract which has the potential for structural diversity as indicated by site-specific cleavage with S1 nuclease is another feature of this region. The organization of this promoter region is compared to that of other cloned members of this family. The potential roles that these sequences may play in the transcriptional regulation of this gene are discussed.
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PMID:Sequence analysis of the 5' flanking region of the human estrogen receptor gene. 147 47

The isolation of a rat hsp 70-related gene which is specifically and highly expressed in testis is described together with the complete nucleotide sequence of the transcription unit (2947 bp), 5' flanking (about 1 kbp) and 3' flanking (about 0.3 kbp) regions. The sequence analysis and nuclease S1 mapping revealed that the isolated gene (referred to as the hst70 gene) represents a novel, distinct member of the hsp70 multigene family. Its transcription unit lacks introns and a single open reading frame encodes a protein of 69.5 kDa. The predicted amino acid sequence of this protein is highly similar (only four out of 633 amino acids are different) to that encoded by the mouse testis-specific hsp70.2 gene (Zakeri, Z.F., Wolgemuth, D.J. and Hunt, C.R. (1988) Mol. Cell. Biol. 8, 2925-2932). The functional significance of multiple potentially regulatory sequences (e.g. TATA-boxes, heat-shock element and estrogen receptor binding site) present in the 5' flanking region of the rat hst70 gene is discussed.
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PMID:Isolation and nucleotide sequence analysis of the rat testis-specific major heat-shock protein (HSP70)-related gene. 168 14

In vitro studies have demonstrated that the estrogen receptor (ER) can bind to the rat PRL estrogen response element (ERE) located 1700 basepairs upstream of the transcriptional start site. However, the mechanism by which the receptor-DNA complex influences the activity of RNA polymerase located in the promoter region is not understood. To begin investigating this process, we developed cell lines derived from GH3 cells that contain steroid-responsive bovine papillomavirus minichromosomes. Within these minichromosomes is a hybrid gene composed of the 5' flanking region of the PRL gene, driving the expression of the Tn5 gene. The episomal PRL DNA sequences responded to 17 beta-estradiol (E2) by increasing the rate of Tn5 gene transcription. Nucleosome mapping experiments using micrococcal nuclease demonstrated that nucleosome-like structures were assembled on the minichromosome in an ordered array separated by 150-200 basepairs of DNA. Novel S1 nuclease as well as DNase-I-hypersensitive sites in the chromatin of the promoter and distal regulatory regions of the episomal PRL gene were detected by indirect end-labeling studies. The nuclease hypersensitive sites in the distal region containing the ERE were modified after treatment of the cells with either E2 or the antiestrogen 4-hydroxytamoxifen. However, only E2 treatment of cells resulted in an increase in the nuclease hypersensitivity of the promoter region and induced gene expression, while antiestrogen treatment had no effect on either parameter. This suggests that complex interactions between factors located at the distal and proximal regulatory regions ultimately determine the transcriptional response of the PRL gene to E2.
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PMID:An interaction between the 5' flanking distal and proximal regulatory domains of the rat prolactin gene is required for transcriptional activation by estrogens. 196 74

The human progesterone receptor (hPR) cDNA, synthesized from T47D breast cancer cells, and the hPR gene 5'-flanking region were cloned and sequenced. Comparison of the cDNA-deduced amino acid sequence with other PR homologues demonstrated the modular structure characteristic of nuclear receptors. As in the case of the chicken homologue, there are two hPR forms, A and B, which originate from translational initiation at AUG2 (codon 165) and AUG1, respectively. Northern blot analysis of T47D mRNA using various cDNA derived probes identified two classes of hPR mRNAs, one of which could code for hPR form B, while the other one lacked the 5' region upstream of AUG1. S1 nuclease mapping and primer extension analyses confirmed that the second class of hPR transcripts are initiated between +737 and +842 and thus encode hPR form A, but not form B. By using the hPR gene 5'-flanking sequences as promoter region in chimeric genes, we show that a functional promoter (located between -711 and +31) directs initiation of hPR mRNAs from the authentic start sites located at +1 and +15. Most importantly, initiation of transcription from chimeric genes demonstrated the existence of a second promoter located between +464 and +1105. Transient co-transfection experiments with vectors expressing the human estrogen receptor showed that both promoters were estrogen inducible, although no classical estrogen responsive element was detected in the corresponding sequences. When transiently expressed, the two hPR forms similarly activated transcription from reporter genes containing a single palindromic progestin responsive element (PRE), while form B was more efficient at activating the PRE of the mouse mammary tumor virus long terminal repeat. Transcription from the ovalbumin promoter, however, was induced by hPR form A, but not by form B.
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PMID:Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. 232 27

Recent studies have identified an estrogen receptor (ER) promoter upstream of the transcriptional start site originally mapped for the ER gene. We have examined promoter use in a number of breast carcinoma cell lines. MCF7, T47D, BT474, and MDA-MB-361 cell lines all use the P0 promoter, whereas BT20 and ZR75-1 do not demonstrate transcription from this upstream start site. S1 nuclease analysis was used to quantitate the amount of ER mRNA originating from the two different promoters. In MCF7, one-third of the ER mRNA results from transcription originating upstream of the major ER promoter and in T47D, 12% of the message originates from upstream transcription. Promoter use was analyzed in human mammary epithelial cells and human late proliferation endometrium. Upstream promoter use was found to be characteristic of human late proliferation endometrium but not human mammary epithelial cells. These results indicated that certain breast carcinomas demonstrate ER transcription from a promoter not normally active in normal breast epithelium. This activation may involve a factor active in normal human endometrium.
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PMID:Quantitative analysis of the transcriptional start sites of estrogen receptor in breast carcinoma. 766 25

In endometrial cancers, some overexpression of estrogen receptor (ER) mRNA occurred in comparison with the ER mRNA level in normal endometria. DNA binding domains (DBDs) of ER mRNA were detected in 100% (13/13) of the endometrial cancers, and a mutated ER-DBD mRNA was found in 3 of the 13 by S1 nuclease protection analysis. It is suggested that estrogen might lead to disorder in the promotion of estrogen-inducible proteins in these 3 endometrial cancers, which seem to have a point-mutated DBD of the ER and a functional steroid-binding domain, resulting in the dedifferentiation of the original cells, and that the development and growth of cancer cells might, in part, be driven by estrogen.
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PMID:Expression of aberrant estrogen receptor mRNA in endometrial cancers in comparison with normal endometria. 799 15

The estrogen receptor, a hormone-regulated transcription factor, regulates gene expression by interacting with a specific nucleotide sequence called the estrogen-responsive element (ERE). In this report we demonstrate by potassium permanganate, osmium tetroxide and diethylpyrocarbonate reactivity and S1 nuclease sensitivity that the nucleotides either within or in the immediate region of imperfect and perfect EREs are in a non-B DNA conformation. The presence of nucleotides in a non-B DNA conformation in the ERE is an intrinsic property of the DNA and is independent of whether the ERE is in linear or supercoiled DNA. S1 nuclease sensitivity was peculiar to the ERE as it was not detected in the thyroid hormone-responsive element. Our results suggest that the nucleotides comprising the ERE are structurally labile. We propose that this intrinsic lability of the ERE could be constrained in vivo such that a unique DNA tertiary structure is formed which may facilitate recognition of the ERE by the estrogen receptor.
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PMID:Estrogen-responsive elements contain non-B DNA. 837 75

Recently, it has been suggested that c-myc expression might correlate with estrogen receptor (ER) status and metastatic spread in ovarian cancer. In this study, expression of c-myc mRNA in 90 epithelial ovarian carcinomas was determined using the S1 nuclease protection assay. Expression of c-myc mRNA was detectable in 27 of 90 tumors. There was no significant association between c-myc mRNA expression and metastatic spread, survival time, FIGO stage, or histologic grade and type. C-myc mRNA was expressed in 45% of ER-positive tumors but only 24% of ER-negative tumors (p = 0.094; Fisher's exact test). Similarly, 44% of progesterone receptor (PR)-positive and 23% of PR-negative tumors expressed c-myc mRNA (p = 0.098). However, the association between c-myc mRNA expression and ER and PR status was not statistically significant. The ratio of mean expression of c-myc mRNA in patients with FIGO stages III/IV compared with patients with FIGO stages I/II was 2.1:1, an insignificant difference (p = 0.57, Wilcoxon rank sum test). In conclusion, c-myc was not significantly associated with the clinical parameters investigated in this study.
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PMID:C-myc mRNA expression in epithelial ovarian carcinomas in relation to estrogen receptor status, metastatic spread, survival time, FIGO stage, and histologic grade and type. 947 95

Using the rapid amplification of complementary DNA ends (RACE) methodology we have identified three new chicken estrogen receptor-alpha (cER alpha) messenger RNA (mRNA) variants in addition to the previously described form (isoform A). Whereas one of the new variants (isoform B) presents a 5'-extremity contiguous to the 5'-end of isoform A, the two other forms (isoforms C and D) are generated by alternative splicing of upstream exons (C and D) to a common site situated 70 nucleotides upstream of the translation start site in the previously assigned exon 1 (A). The 3'-end of exon 1C has been located at position -1334 upstream of the transcription start site of the A isoform (+1). Whereas the genomic location of exon 1D is unknown, 700 bp 5' to this exon were isolated by genomic walking, and their sequence was determined. The transcription start sites of the cER alpha mRNA isoforms were defined. In transfection experiments, the regions immediately upstream of the A-D cER alpha mRNA isoforms were shown to possess cell-specific promoter activities. Three of these promoters were down-regulated in the presence of estradiol and ER alpha protein. It is concluded, therefore, that the expression of the four different cER alpha mRNA isoforms is under the control of four different promoters. Finally, RT-PCR, S1 nuclease mapping, and primer extension analysis of these different cER alpha mRNA isoforms revealed a differential pattern of expression of the cER alpha gene in chicken tissues. Together, the results suggest that alternative 5'-splicing and promoter usage may be mechanisms used to modulate the levels of expression of the chicken ER alpha gene in a tissue-specific and/or developmental stage-specific manner.
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PMID:Identification of novel chicken estrogen receptor-alpha messenger ribonucleic acid isoforms generated by alternative splicing and promoter usage. 979 73

The isolation and characterization of several new human estrogen receptor-alpha (hERalpha) mRNAs are described. Together with those previously identified, they give rise to a total of six hERalpha mRNA isoforms (A-F hERalpha mRNAs). Produced from a single hERalpha gene by multiple promoter usage, all these transcripts encode a common protein but differ in their 5'-untranslated region as a consequence of alternative splicing of five upstream exons (1B-1F). RT-PCR and S1 nuclease mapping analysis of these different hERalpha mRNA isoforms revealed a differential pattern of expression of the hERalpha gene in human tissues and cell types. The A hERalpha mRNA is the main isoform detected in mammary glands or in the tumor cell lines derived from this tissue. In endometrium, the predominant forms are the A and C hERalpha mRNA isoforms, whereas the C and F hERalpha mRNA isoforms are the major forms detected in ovary. Finally, high levels of the E hERalpha mRNA isoform are restricted to the liver with an increased expression in females. Taken together, our results demonstrate that the hERalpha gene is a complex genomic unit exhibiting alternative splicing and promoter usage in a tissue-specific manner.
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PMID:Differentially expressed messenger RNA isoforms of the human estrogen receptor-alpha gene are generated by alternative splicing and promoter usage. 984 67


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