Analysis of the distal 5′ region of the humanCYP17gene

Genome ◽  
1995 ◽  
Vol 38 (5) ◽  
pp. 845-849 ◽  
Author(s):  
Sepehr Steve Maghsoudlou ◽  
Timothy R. Hughes ◽  
Peter J. Hornsby
Keyword(s):  
Copy Number ◽  
Regulatory Elements ◽  
Endogenous Retrovirus ◽  
Upstream Region ◽  
Human Endogenous Retrovirus ◽  
Regulatory Sequences ◽  
Cyp17 Gene ◽  
Low Copy Number ◽  
Methyltransferase Gene ◽  
Flanking Region

In order to search for additional regulatory elements in the human CYP17 (steroid 17α-hydroxylase) gene and to compare it with potential regulatory elements in bovine CYP17 genes, 3.5 kb of 5′ flanking region of CYP17 was cloned and analyzed. The newly acquired sequence was shown to be a highly defective copy of the human endogenous retrovirus HERV-K family. This retroviral sequence was itself interrupted by a novel element, a low copy number repeat occurring about 20 times in the human genome, including a known copy in the human catechol-O-methyltransferase gene. A reanalysis of the entire 5′ flanking region of human CYP17 indicates that only the 300 bp immediately distal to the promoter is of unique sequence; other regulatory sequences, including any that are similar to the upstream region of the bovine genes, are unlikely to occur within 5.5 kb of the promoter.Key words: Human CYP17 gene, endogenous retrovirus, low-copy-number repeats.

Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene

1986 ◽  
Vol 6 (12) ◽  
pp. 4548-4557
Author(s):  
J Hirsh ◽  
B A Morgan ◽  
S B Scholnick
Keyword(s):  
Drosophila Melanogaster ◽  
Germ Line ◽  
Regulatory Elements ◽  
P Element ◽  
Developmental Expression ◽  
Upstream Region ◽  
Regulatory Sequences ◽  
Flanking Sequences

We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes lacking these sequences could be expressed at 10 to 50% of wild-type levels at specific developmental times. These genes showed components of normal developmental expression, which suggests that they retain some regulatory elements. All Ddc genes lacking the normal immediate 5'-flanking sequences were grossly deficient in larval central nervous system expression. Thus, this upstream region must contain at least one element necessary for this expression. A mutated Ddc gene without a normal TATA boxlike sequence used the normal RNA start points, indicating that this sequences is not required for start point specificity.

Regulatory elements in the 5'-flanking region and the first intron contribute to transcriptional control of the mouse alpha 1 type I collagen gene

1989 ◽  
Vol 9 (5) ◽  
pp. 2224-2227
Author(s):  
R A Rippe ◽  
S I Lorenzen ◽  
D A Brenner ◽  
M Breindl
Keyword(s):  
Transcriptional Control ◽  
Type I Collagen ◽  
Regulatory Elements ◽  
Regulatory Sequences ◽  
Type I ◽  
Col1a1 Gene ◽  
First Intron ◽  
Flanking Region ◽  
Specific Regulation ◽  
High Level

We have identified two blocks of regulatory sequences located in the 5'-flanking region and the first intron of the mouse alpha 1 type I collagen (COL1A1) gene. Both blocks were found to contain positive as well as negative regulatory elements. Sequences located within 222 base pairs upstream of the transcription start site showed a strong stimulatory effect on the COL1A1 promoter and were sufficient for tissue-specific regulation of the COL1A1 gene. The combined upstream and intron regulatory sequences showed a marked inhibition of COL1A1 promoter activity in fibroblasts. This finding suggests that additional, more remote regulatory sequences may be required for establishing the high level of activity of the endogenous COL1A1 gene in fibroblastoid cells.

scholarly journals Common core sequences are found in skeletal muscle slow- and fast-fiber-type-specific regulatory elements.

1996 ◽  
Vol 16 (5) ◽  
pp. 2408-2417 ◽  
Author(s):  
M Nakayama ◽  
J Stauffer ◽  
J Cheng ◽  
S Banerjee-Basu ◽  
E Wawrousek ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Upstream Region ◽  
Regulatory Sequences ◽  
Fast Fiber ◽  
Core Elements

The molecular mechanisms generating muscle diversity during development are unknown. The phenotypic properties of slow- and fast-twitch myofibers are determined by the selective transcription of genes coding for contractile proteins and metabolic enzymes in these muscles, properties that fail to develop in cultured muscle. Using transgenic mice, we have identified regulatory elements in the evolutionarily related troponin slow (TnIs) and fast (TnIf) genes that confer specific transcription in either slow or fast muscles. Analysis of serial deletions of the rat TnIs upstream region revealed that sequences between kb -0.95 and -0.5 are necessary to confer slow-fiber-specific transcription; the -0.5-kb fragment containing the basal promoter was inactive in five transgenic mouse lines tested. We identified a 128-bp regulatory element residing at kb -0.8 that, when linked to the -0.5-kb TnIs promoter, specifically confers transcription to slow-twitch muscles. To identify sequences directing fast-fiber-specific transcription, we generated transgenic mice harboring a construct containing the TnIs kb -0.5 promoter fused to a 144-bp enhancer derived from the quail TnIf gene. Mice harboring the TnIf/TnIs chimera construct expressed the transgene in fast but not in slow muscles, indicating that these regulatory elements are sufficient to confer fiber-type-specific transcription. Alignment of rat TnIs and quail TnIf regulatory sequences indicates that there is a conserved spatial organization of core elements, namely, an E box, a CCAC box, a MEF-2-like sequence, and a previously uncharacterized motif. The core elements were shown to bind their cognate factors by electrophoretic mobility shift assays, and their mutation demonstrated that the TnIs CCAC and E boxes are necessary for transgene expression. Our results suggest that the interaction of closely related transcriptional protein-DNA complexes is utilized to specify fiber type diversity.

scholarly journals ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription

2021 ◽  
Author(s):  
Chunhong Yu ◽  
Xiaoyun Lei ◽  
Fang Chen ◽  
Song Mao ◽  
Lu Lv ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Suppressors ◽  
Target Genes ◽  
Critical Role ◽  
Endogenous Retrovirus ◽  
Early Embryogenesis ◽  
Human Endogenous Retrovirus ◽  
Regulatory Sequences ◽  
3D Architecture

The transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge. Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.

scholarly journals The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e53623 ◽  
Author(s):  
Marta Garcia-Montojo ◽  
María Dominguez-Mozo ◽  
Ana Arias-Leal ◽  
Ángel Garcia-Martinez ◽  
Virginia De las Heras ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Severity ◽  
Copy Number ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Dna Copy Number ◽  
Multiple Sclerosis Patients

Unreliable Real-Time PCR Analysis of Human Endogenous Retrovirus-W (HERV-W) RNA Expression and DNA Copy Number in Multiple Sclerosis

2009 ◽  
Vol 25 (3) ◽  
pp. 377-378 ◽  
Author(s):  
Jeremy A. Garson ◽  
Jim F. Huggett ◽  
Stephen A. Bustin ◽  
Michael W. Pfaffl ◽  
Vladimir Benes ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real Time ◽  
Real Time Pcr ◽  
Copy Number ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Pcr Analysis ◽  
Rna Expression ◽  
Dna Copy Number

scholarly journals Regulatory elements in the 5'-flanking region and the first intron contribute to transcriptional control of the mouse alpha 1 type I collagen gene.

1989 ◽  
Vol 9 (5) ◽  
pp. 2224-2227 ◽  
Author(s):  
R A Rippe ◽  
S I Lorenzen ◽  
D A Brenner ◽  
M Breindl
Keyword(s):  
Transcriptional Control ◽  
Type I Collagen ◽  
Regulatory Elements ◽  
Regulatory Sequences ◽  
Type I ◽  
Col1a1 Gene ◽  
First Intron ◽  
Flanking Region ◽  
Specific Regulation ◽  
High Level

We have identified two blocks of regulatory sequences located in the 5'-flanking region and the first intron of the mouse alpha 1 type I collagen (COL1A1) gene. Both blocks were found to contain positive as well as negative regulatory elements. Sequences located within 222 base pairs upstream of the transcription start site showed a strong stimulatory effect on the COL1A1 promoter and were sufficient for tissue-specific regulation of the COL1A1 gene. The combined upstream and intron regulatory sequences showed a marked inhibition of COL1A1 promoter activity in fibroblasts. This finding suggests that additional, more remote regulatory sequences may be required for establishing the high level of activity of the endogenous COL1A1 gene in fibroblastoid cells.

scholarly journals Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene.

1986 ◽  
Vol 6 (12) ◽  
pp. 4548-4557 ◽  
Author(s):  
J Hirsh ◽  
B A Morgan ◽  
S B Scholnick
Keyword(s):  
Drosophila Melanogaster ◽  
Germ Line ◽  
Regulatory Elements ◽  
P Element ◽  
Developmental Expression ◽  
Upstream Region ◽  
Regulatory Sequences ◽  
Flanking Sequences

We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes lacking these sequences could be expressed at 10 to 50% of wild-type levels at specific developmental times. These genes showed components of normal developmental expression, which suggests that they retain some regulatory elements. All Ddc genes lacking the normal immediate 5'-flanking sequences were grossly deficient in larval central nervous system expression. Thus, this upstream region must contain at least one element necessary for this expression. A mutated Ddc gene without a normal TATA boxlike sequence used the normal RNA start points, indicating that this sequences is not required for start point specificity.

scholarly journals Myeloma mutant with a novel 3' flanking region: loss of normal sequence and insertion of repetitive elements leads to decreased transcription but normal processing of the alpha heavy-chain gene products.

1986 ◽  
Vol 6 (6) ◽  
pp. 1903-1916 ◽  
Author(s):  
P D Gregor ◽  
S L Morrison
Keyword(s):  
Copy Number ◽  
Direct Repeat ◽  
Repetitive Elements ◽  
Ecori Fragment ◽  
Chain Gene ◽  
S1 Nuclease ◽  
Low Copy Number ◽  
Negative Effect ◽  
Cleavage And Polyadenylation ◽  
Flanking Region

We isolated and characterized LP1.2, a mouse myeloma mutant with a deletion of at least 4 kilobases (kb) immediately 3' of the alpha gene and introduction of at least 5 kb of novel (nonimmunoglobulin) sequence in its place. A 6.2-kb genomic EcoRI fragment from the mutated allele was cloned, and a subfragment was sequenced. The deletion begins 11 base pairs (bp) beyond the normal site of cleavage and polyadenylation for the secreted form of alpha mRNA. A short direct repeat, eight copies of the 17-mer GCCT ATAGAAGTAAGGA, is located at the junction of the alpha and novel sequences. The first 4 bp of the 17-mer are identical to the last 4 bp of the alpha sequence. Novel sequences downstream of the direct repeats in LP1.2 include a low-copy-number sequence flanked by two distinct, highly repetitive elements. The low-copy-number portion of the novel sequence appears on a single 30-kb EcoRI fragment in several myelomas and in liver DNA; one copy of this fragment has rearranged in cell line W3129, and this allele has rearranged a second time in LP1.2. LP1.2 contains low levels of apparently normal alpha protein and mRNA. The S1 nuclease protection of nuclear and cytoplasmic RNAs shows that cleavage and polyadenylation are efficient and accurate and that they occur without the accumulation of aberrant transcripts. Alpha transcription in isolated nuclei is decreased sevenfold in LP1.2 relative to its parent, which accounts for the low steady-state levels of cytoplasmic alpha mRNA and protein in LP1.2. Decreased alpha transcription could result either from the deletion of a positive regulator in the 3' flanking region or from the introduction of novel sequences which exert a negative effect.

scholarly journals Further Evidence that Human Endogenous Retrovirus K102 is a Replication Competent Foamy Virus that may Antagonize HIV-1 Replication

2015 ◽  
Vol 9 (1) ◽  
pp. 112-122 ◽  
Author(s):  
Marian P. Laderoute ◽  
Louise J. Larocque ◽  
Antonio Giulivi ◽  
Francisco Diaz-Mitoma
Keyword(s):  
Copy Number ◽  
Particle Production ◽  
Mononuclear Cells ◽  
Foamy Virus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Western Blots ◽  
Genomic Copy Number ◽  
Genomic Copy ◽  
Hiv 1

Objective:The goals of the research were to determine if a foamy effect on macrophages was due to human endogenous retrovirus K102 (HERV-K102) replication, and to further address its potential significance in HIV-1 infection.Methods:An RT-PCR HERV-K HML-2 pol method was used to screen the unknown HERV, and isolated bands were sent for sequencing. Confirmation of RNA expression was performed by a real time quantitative PCR (qPCR) pol ddCt method. Rabbit antibodies to Env peptides were used to assess expression by immunohistology and processing of Env by western blots. A qPCR pol ddCt method to ascertain genomic copy number was performed on genomic DNA isolated from plasma comparing HIV-1 exposed seronegative (HESN) commercial sex workers (CSW) to normal controls and contrasted with HIV-1 patients.Results:HERV-K102 expression, particle production and replication were associated with foamy macrophage generation in the cultures of cord blood mononuclear cells under permissive conditions. A five-fold increased HERV-K102 pol genomic copy number was found in the HESN cohort over normal which was not found in HIV-1 positive patients (p=0.0005).Conclusions:This work extends the evidence that HERV-K102 has foamy virus attributes, is replication competent, and is capable of high replication rate in vivo and in vitro. This may be the first characterization of a replication-competent, foamy-like virus of humans. High particle production inferred by increased integration in the HESN cohort over HIV-1 patients raises the issue of the clinical importance of HERV-K102 particle production as an early protective innate immune response against HIV-1 replication.

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