• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Dec 1987; 84(24): 8869–8873.
PMCID: PMC299652

Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene.

Abstract

Several lines of evidence have suggested that the regulation of type I collagen gene transcription is complex and that important regulatory elements reside 5' to, and within, the first intron of the alpha 1(I) gene. We therefore sequenced a 2.3-kilobase HindIII fragment that encompasses 804 base pairs of 5' flanking sequence, the first exon, and most of the first intron of the alpha 1(I) human collagen gene. A 274-base-pair intronic sequence, flanked by Ava I sites (A274), contained a sequence identical to a high-affinity decanucleotide binding site for transcription factor Sp1 and a viral core enhancer sequence. DNase I protection experiments indicated zones of protection that corresponded to these motifs. When A274 was cloned 5' to the chloramphenicol acetyltransferase (CAT) gene, driven by an alpha 1(I) collagen promoter sequence, and expression was assessed by transfection, significant orientation-specific inhibition of CAT activity was observed. This effect was most apparent in chicken tendon fibroblasts, which modulate their level of collagen synthesis in culture. We propose that normal regulation of alpha 1(I) collagen gene transcription results from an interplay of positive and negative elements present in the promoter region and within the first intron.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Avvedimento E, Yamada Y, Lovelace E, Vogeli G, de Crombrugghe B, Pastan I. Decrease in the levels of nuclear RNA precursors for alpha 2 collagen in Rous sarcoma virus transformed fibroblasts. Nucleic Acids Res. 1981 Mar 11;9(5):1123–1131. [PMC free article] [PubMed]
  • Sandmeyer S, Gallis B, Bornstein P. Coordinate transcriptional regulation of type I procollagen genes by Rous sarcoma virus. J Biol Chem. 1981 May 25;256(10):5022–5028. [PubMed]
  • Schmidt A, Setoyama C, de Crombrugghe B. Regulation of a collagen gene promoter by the product of viral mos oncogene. Nature. 1985 Mar 21;314(6008):286–289. [PubMed]
  • Schmidt A, Rossi P, de Crombrugghe B. Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression. Mol Cell Biol. 1986 Feb;6(2):347–354. [PMC free article] [PubMed]
  • Schnieke A, Harbers K, Jaenisch R. Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene. Nature. 304(5924):315–320. [PubMed]
  • Harbers K, Kuehn M, Delius H, Jaenisch R. Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1504–1508. [PMC free article] [PubMed]
  • Breindl M, Harbers K, Jaenisch R. Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure. Cell. 1984 Aug;38(1):9–16. [PubMed]
  • Barsh GS, Roush CL, Gelinas RE. DNA and chromatin structure of the human alpha 1 (I) collagen gene. J Biol Chem. 1984 Dec 10;259(23):14906–14913. [PubMed]
  • Merlino GT, McKeon C, de Crombrugghe B, Pastan I. Regulation of the expression of genes encoding types I, II, and III collagen during chick embryonic development. J Biol Chem. 1983 Aug 25;258(16):10041–10048. [PubMed]
  • Jähner D, Jaenisch R. Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature. 1985 Jun 13;315(6020):594–597. [PubMed]
  • Hartung S, Jaenisch R, Breindl M. Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. Nature. 320(6060):365–367. [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Hearing P, Shenk T. The adenovirus type 5 E1A transcriptional control region contains a duplicated enhancer element. Cell. 1983 Jul;33(3):695–703. [PubMed]
  • Weiher H, König M, Gruss P. Multiple point mutations affecting the simian virus 40 enhancer. Science. 1983 Feb 11;219(4585):626–631. [PubMed]
  • Wildeman AG, Sassone-Corsi P, Grundström T, Zenke M, Chambon P. Stimulation of in vitro transcription from the SV40 early promoter by the enhancer involves a specific trans-acting factor. EMBO J. 1984 Dec 20;3(13):3129–3133. [PMC free article] [PubMed]
  • Norrander J, Kempe T, Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. [PubMed]
  • Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Chu ML, de Wet W, Bernard M, Ramirez F. Fine structural analysis of the human pro-alpha 1 (I) collagen gene. Promoter structure, AluI repeats, and polymorphic transcripts. J Biol Chem. 1985 Feb 25;260(4):2315–2320. [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. [PMC free article] [PubMed]
  • Piette J, Kryszke MH, Yaniv M. Specific interaction of cellular factors with the B enhancer of polyoma virus. EMBO J. 1985 Oct;4(10):2675–2685. [PMC free article] [PubMed]
  • Augereau P, Chambon P. The mouse immunoglobulin heavy-chain enhancer: effect on transcription in vitro and binding of proteins present in HeLa and lymphoid B cell extracts. EMBO J. 1986 Aug;5(8):1791–1797. [PMC free article] [PubMed]
  • Duksin D, Bornstein P. Impaired conversion of procollagen to collagen by fibroblasts and bone treated with tunicamycin, an inhibitor of protein glycosylation. J Biol Chem. 1977 Feb 10;252(3):955–962. [PubMed]
  • Schwarz RI, Bissell MJ. Dependence of the differentiated state on the cellular environment: modulation of collagen synthesis in tendon cells. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4453–4457. [PMC free article] [PubMed]
  • Chu ML, de Wet W, Bernard M, Ding JF, Morabito M, Myers J, Williams C, Ramirez F. Human pro alpha 1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons. Nature. 310(5975):337–340. [PubMed]
  • Briggs MR, Kadonaga JT, Bell SP, Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. [PubMed]
  • Liau G, Yamada Y, de Crombrugghe B. Coordinate regulation of the levels of type III and type I collagen mRNA in most but not all mouse fibroblasts. J Biol Chem. 1985 Jan 10;260(1):531–536. [PubMed]
  • Schmidt A, Yamada Y, de Crombrugghe B. DNA sequence comparison of the regulatory signals at the 5' end of the mouse and chick alpha 2 type I collagen genes. J Biol Chem. 1984 Jun 25;259(12):7411–7415. [PubMed]
  • Yamada Y, Mudryj M, de Crombrugghe B. A uniquely conserved regulatory signal is found around the translation initiation site in three different collagen genes. J Biol Chem. 1983 Dec 25;258(24):14914–14919. [PubMed]
  • Liau G, Mudryj M, de Crombrugghe B. Identification of the promoter and first exon of the mouse alpha 1 (III) collagen gene. J Biol Chem. 1985 Mar 25;260(6):3773–3777. [PubMed]
  • McKeon C, Schmidt A, de Crombrugghe B. A sequence conserved in both the chicken and mouse alpha 2(I) collagen promoter contains sites sensitive to S1 nuclease. J Biol Chem. 1984 May 25;259(10):6636–6640. [PubMed]
  • Schlokat U, Bohmann D, Schöler H, Gruss P. Nuclear factors binding specific sequences within the immunoglobulin enhancer interact differentially with other enhancer elements. EMBO J. 1986 Dec 1;5(12):3251–3258. [PMC free article] [PubMed]
  • Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature. 1986 Aug 21;322(6081):697–701. [PubMed]
  • Rossi P, de Crombrugghe B. Identification of a cell-specific transcriptional enhancer in the first intron of the mouse alpha 2 (type I) collagen gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5590–5594. [PMC free article] [PubMed]
  • Horton W, Miyashita T, Kohno K, Hassell JR, Yamada Y. Identification of a phenotype-specific enhancer in the first intron of the rat collagen II gene. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8864–8868. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...