Elements in the First Intron of the Alpha 1(I) Collagen Gene Interact with Sp1 to Regulate Gene Expression

Overview

Journal Gene Expr

Specialty Molecular Biology

Date 1992 Jan 1

PMID 1472870

Citations 4

Authors

D J Liska

V R Robinson

P Bornstein

Affiliations

Soon will be listed here.

Abstract

Sequences within the first intron of the alpha 1(I) collagen gene act both positively and negatively to regulate expression of the gene. We have further characterized a 274 bp intronic sequence that contains an orientation-specific inhibitory activity and represents a constitutive DNase I-hypersensitive site in the gene. We show that this sequence contains two tandem, unique binding elements for the transcription factor Sp1. In addition, an Sp1-like site, capable of competing for protein binding to the intronic elements, resides in the distal promoter of the collagen gene. The results of experiments with site-directed mutations that abolish binding to the intronic elements indicate that these protein-DNA interactions have an inhibitory effect on the transcriptional efficiency of alpha 1(I) collagen-reporter gene constructs in transient transfection analysis. These data support our conclusion that the first intron plays a complex role, involving multiple protein-DNA binding interactions, in the regulation of expression of the alpha 1(I) collagen gene.

Citing Articles

Noncoding sequence variants define a novel regulatory element in the first intron of the N-acetylglutamate synthase gene.

Haberle J, Moore M, Haskins N, Rufenacht V, Rokicki D, Rubio-Gozalbo E Hum Mutat. 2021; 42(12):1624-1636.

PMID: 34510628 PMC: 8604755. DOI: 10.1002/humu.24281.

A gene-targeting approach identifies a function for the first intron in expression of the alpha1(I) collagen gene.

Hormuzdi S, Penttinen R, Jaenisch R, Bornstein P Mol Cell Biol. 1998; 18(6):3368-75.

PMID: 9584177 PMC: 108918. DOI: 10.1128/MCB.18.6.3368.

Transcriptional activation of the minimal human Proalpha1(I) collagen promoter: obligatory requirement for Sp1.

Poppleton H, Raghow R Biochem J. 1997; 323 ( Pt 1):225-31.

PMID: 9173885 PMC: 1218298. DOI: 10.1042/bj3230225.

Cell-specific expression of alpha 1(I) collagen-hGH minigenes in transgenic mice.

Liska D, Reed M, Sage E, Bornstein P J Cell Biol. 1994; 125(3):695-704.

PMID: 8175887 PMC: 2119997. DOI: 10.1083/jcb.125.3.695.

References

Li R, Knight J, Jackson S, Tjian R, Botchan M . Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription. Cell. 1991; 65(3):493-505. DOI: 10.1016/0092-8674(91)90467-d. View

Gidoni D, Kadonaga J, Barrera-Saldana H, Takahashi K, Chambon P, Tjian R . Bidirectional SV40 transcription mediated by tandem Sp1 binding interactions. Science. 1985; 230(4725):511-7. DOI: 10.1126/science.2996137. View

Gross D, Garrard W . Nuclease hypersensitive sites in chromatin. Annu Rev Biochem. 1988; 57:159-97. DOI: 10.1146/annurev.bi.57.070188.001111. View

Nehls M, Rippe R, Veloz L, Brenner D . Transcription factors nuclear factor I and Sp1 interact with the murine collagen alpha 1 (I) promoter. Mol Cell Biol. 1991; 11(8):4065-73. PMC: 361214. DOI: 10.1128/mcb.11.8.4065-4073.1991. View

McKnight S, Tjian R . Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986; 46(6):795-805. DOI: 10.1016/0092-8674(86)90061-9. View

Buchanan R, Gralla J . Factor interactions at simian virus 40 GC-box promoter elements in intact nuclei. Mol Cell Biol. 1987; 7(4):1554-8. PMC: 365246. DOI: 10.1128/mcb.7.4.1554-1558.1987. View

Lemaigre F, Courtois S, Lafontaine D, Rousseau G . Evidence that the upstream stimulatory factor and the Sp1 transcription factor bind in vitro to the promoter of the human-growth-hormone gene. Eur J Biochem. 1989; 181(3):555-61. DOI: 10.1111/j.1432-1033.1989.tb14760.x. View

Chan H, Hartung S, Breindl M . Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation. Mol Cell Biol. 1991; 11(1):47-54. PMC: 359585. DOI: 10.1128/mcb.11.1.47-54.1991. View

Bornstein P, McKay J, Liska D, Apone S, Devarayalu S . Interactions between the promoter and first intron are involved in transcriptional control of alpha 1(I) collagen gene expression. Mol Cell Biol. 1988; 8(11):4851-7. PMC: 365578. DOI: 10.1128/mcb.8.11.4851-4857.1988. View

10.

Olsen A, Geddis A, Prockop D . High levels of expression of a minigene version of the human pro alpha 1 (I) collagen gene in stably transfected mouse fibroblasts. Effects of deleting putative regulatory sequences in the first intron. J Biol Chem. 1991; 266(2):1117-21. View

11.

Rossouw C, Vergeer W, du Plooy S, Bernard M, Ramirez F, de Wet W . DNA sequences in the first intron of the human pro-alpha 1(I) collagen gene enhance transcription. J Biol Chem. 1987; 262(31):15151-7. View

12.

Schnieke A, Harbers K, Jaenisch R . Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene. Nature. 1983; 304(5924):315-20. DOI: 10.1038/304315a0. View

13.

Bornstein P, McKay J, Morishima J, Devarayalu S, Gelinas R . Regulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene. Proc Natl Acad Sci U S A. 1987; 84(24):8869-73. PMC: 299652. DOI: 10.1073/pnas.84.24.8869. View

14.

Briggs M, Kadonaga J, Bell S, Tjian R . Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986; 234(4772):47-52. DOI: 10.1126/science.3529394. View

15.

Boast S, Su M, Ramirez F, Sanchez M, Avvedimento E . Functional analysis of cis-acting DNA sequences controlling transcription of the human type I collagen genes. J Biol Chem. 1990; 265(22):13351-6. View

16.

Barsh G, Roush C, Gelinas R . DNA and chromatin structure of the human alpha 1 (I) collagen gene. J Biol Chem. 1984; 259(23):14906-13. View

17.

Slack J, Liska D, Bornstein P . An upstream regulatory region mediates high-level, tissue-specific expression of the human alpha 1(I) collagen gene in transgenic mice. Mol Cell Biol. 1991; 11(4):2066-74. PMC: 359894. DOI: 10.1128/mcb.11.4.2066-2074.1991. View

18.

Bornstein P, SAGE H . Regulation of collagen gene expression. Prog Nucleic Acid Res Mol Biol. 1989; 37:67-106. DOI: 10.1016/s0079-6603(08)60695-9. View

19.

Courey A, Holtzman D, Jackson S, Tjian R . Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell. 1989; 59(5):827-36. DOI: 10.1016/0092-8674(89)90606-5. View

20.

Rippe R, Lorenzen S, Brenner D, Breindl M . Regulatory elements in the 5'-flanking region and the first intron contribute to transcriptional control of the mouse alpha 1 type I collagen gene. Mol Cell Biol. 1989; 9(5):2224-7. PMC: 363018. DOI: 10.1128/mcb.9.5.2224-2227.1989. View