Regulation of expression of the α 1 (1) collagen gene: A critical appraisal of the role of the first intron

Sequences within the first intron of the alpha 1(I) collagen gene have been implicated in the regulation of expression of alpha 1(I) collagen-reporter gene constructs in cultured cells. However, the physiological significance of these intronic elements has not been established. We have used in situ hybridization to examine whether a cell-specific pattern of expression of human alpha 1(I) collagen-human growth hormone minigenes exists in transgenic mice. Our results indicate that transgenes which contained 2,300 bp of promoter/5' flanking sequence and an intact first intron were well expressed by fibroblasts in dermis and fascia, whereas transgenes lacking the intronic sequence, +292 to +1440, were not expressed in dermis and poorly expressed in fascia. Analysis of transgene expression in cultured fibroblasts obtained from dermal explants of transgenic animals confirmed the requirement for these intronic sequences in the regulation of the alpha 1(I) collagen gene. In contrast, transgenes with or without the intronic deletion were expressed equally well in tendon and bone, in a manner comparable to the endogenous mouse alpha 1(I) collagen gene, and expression of neither transgene was detected in skeletal muscle or perichondrium. These data support a model in which cis-acting elements in the first intron, and their cognate DNA-binding proteins, mediate transcription of the alpha 1(I) collagen gene in some cells, such as dermal fibroblasts, but not in tendon cells or osteoblasts. Moreover, regions of the gene not included in the sequence, -2300 to +1440, appear to be required for transcription in tissues such as skeletal muscle and perichondrium.

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935: Critical Appraisal of the Role of Ureteroscopy in Treatment of Pediatric Renal and Ureteric Calculi

The Journal of Urology ◽

10.1016/s0022-5347(18)31163-7 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 310-310

Author(s):

Sumit Dave ◽

Luis H. Braga ◽

Antoine E. Khoury ◽

Walid A. Farhat

Keyword(s):

Critical Appraisal ◽

Ureteric Calculi

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Understanding the nature and scope of clinical research commentaries in PubMed

Journal of the American Medical Informatics Association ◽

10.1093/jamia/ocz209 ◽

2019 ◽

Vol 27 (3) ◽

pp. 449-456

Author(s):

James R Rogers ◽

Hollis Mills ◽

Lisa V Grossman ◽

Andrew Goldstein ◽

Chunhua Weng

Keyword(s):

Clinical Research ◽

Sentiment Analysis ◽

Random Sample ◽

Full Text ◽

Topic Modeling ◽

Critical Appraisal ◽

Research Articles ◽

Disease Specific ◽

Research Studies

Abstract Scientific commentaries are expected to play an important role in evidence appraisal, but it is unknown whether this expectation has been fulfilled. This study aims to better understand the role of scientific commentary in evidence appraisal. We queried PubMed for all clinical research articles with accompanying comments and extracted corresponding metadata. Five percent of clinical research studies (N = 130 629) received postpublication comments (N = 171 556), resulting in 178 882 comment–article pairings, with 90% published in the same journal. We obtained 5197 full-text comments for topic modeling and exploratory sentiment analysis. Topics were generally disease specific with only a few topics relevant to the appraisal of studies, which were highly prevalent in letters. Of a random sample of 518 full-text comments, 67% had a supportive tone. Based on our results, published commentary, with the exception of letters, most often highlight or endorse previous publications rather than serve as a prominent mechanism for critical appraisal.

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Identification of an enhancer sequence within the first intron required for cartilage-specific transcription of the α2(XI) collagen gene. VOLUME 275 (2000) PAGES 12712-12718

Journal of Biological Chemistry ◽

10.1074/jbc.a012712200 ◽

2009 ◽

Vol 284 (17) ◽

pp. 11748.2-11748 ◽

Cited By ~ 1

Author(s):

Ying Liu ◽

Haochuan Li ◽

Kazuhiro Tanaka ◽

Noriyuki Tsumaki ◽

Yoshihiko Yamada

Keyword(s):

Collagen Gene ◽

Enhancer Sequence ◽

First Intron

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The transcriptional tissue specificity of the human proα1(I) collagen gene is determined by a negative cis-regulatory element in the promoter

Biochemical Journal ◽

10.1042/bj2860179 ◽

1992 ◽

Vol 286 (1) ◽

pp. 179-185 ◽

Cited By ~ 24

Author(s):

C P Simkevich ◽

J P Thompson ◽

H Poppleton ◽

R Raghow

Keyword(s):

Tissue Specificity ◽

Regulatory Element ◽

Mesenchymal Cell ◽

Cell Types ◽

Regulatory Elements ◽

Negative Influence ◽

Collagen Gene ◽

Specific Expression ◽

Cis Acting ◽

First Intron

The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549-2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5′-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription.

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A critical appraisal of the role of respiratory supercomplexes in mitochondria

Biological Chemistry ◽

10.1515/hsz-2012-0317 ◽

2013 ◽

Vol 394 (5) ◽

pp. 631-639 ◽

Cited By ~ 29

Author(s):

Maria Luisa Genova ◽

Giorgio Lenaz

Keyword(s):

Critical Appraisal ◽

Dynamic Equilibrium ◽

Coenzyme Q ◽

Mitochondrial Respiratory Chain ◽

Substantial Evidence ◽

Mammalian Mitochondria ◽

Respiratory Supercomplexes ◽

Functional Relevance ◽

The Individual

Abstract Substantial evidence exists that the mitochondrial respiratory chain is organized in supramolecular units called supercomplexes or respirasomes. While the structural evidence of the supercomplexes is overwhelming, fewer studies have focused on their functional relevance. Although the presence of coenzyme Q channeling between complexes I and III has been ascertained, no such clear demonstration has been carried out for cytochrome c between complexes III and IV, at least in mammalian mitochondria. This review also discusses the implications concerning the number of respiratory complexes organized in supercomplexes and the possibility that they represent associations in dynamic equilibrium with the individual complexes.

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One of the tightly clustered genes of the mouse surfeit locus is a highly expressed member of a multigene family whose other members are predominantly processed pseudogenes.

Molecular and Cellular Biology ◽

10.1128/mcb.8.9.3898 ◽

1988 ◽

Vol 8 (9) ◽

pp. 3898-3905 ◽

Cited By ~ 21

Author(s):

C Huxley ◽

T Williams ◽

M Fried

Keyword(s):

Multigene Family ◽

Open Reading Frame ◽

The Other ◽

Base Pairs ◽

Regulation Of Expression ◽

Reading Frame ◽

Processed Pseudogenes ◽

Dna Fragment ◽

Basic Polypeptide

The mouse surfeit locus is unusual in that it contains a number of closely clustered genes (Surf-1, -2, and -4) that alternate in their direction of transcription (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988). The heterogeneous 5' ends of Surf-1 and Surf-2 are separated by 15 to 73 base pairs (bp), and the 3' ends of Surf-2 and Surf-4 overlap by 133 bp (T. Williams and M. Fried, Mol. Cell. Biol. 6:4558-4569, 1986; T. Williams and M. Fried, Nature (London) 322:275-279, 1986). A fourth gene in this locus, Surf-3, which is a member of a multigene family, has been identified. The poly(A) addition site of Surf-3 lies only 70 bp from the poly(A) addition site of Surf-1. Transcription of Surf-3 has been studied in the absence of the other members of its multigene family after transfection of a cloned genomic mouse DNA fragment, containing the Surf-3 gene, into heterologous monkey cells. Surf-3 specifies a highly expressed 1.0-kilobase mRNA that contains a long open reading frame of 266 amino acids, which would encode a highly basic polypeptide (23% Arg plus Lys). The other members of the Surf-3 multigene family are predominantly, if not entirely, intronless pseudogenes with the hallmarks of being generated by reverse transcription. The role of the very tight clustering on regulation of expression of the genes in the surfeit locus is discussed.

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