Regulatory elements in the first intron contribute to transcriptional control of the human. cap alpha. 1(I) collagen gene
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 ..cap alpha..1(I) gene. The authors 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 ..cap 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 ..cap 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. They propose that normal regulation of ..cap 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.
- Research Organization:
- Univ. of Washington, Seattle (USA)
- OSTI ID:
- 6218270
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:24
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
COLLAGEN
GENE REGULATION
DNA
AUTORADIOGRAPHY
GENES
DNA SEQUENCING
BIOSYNTHESIS
CHLORAMPHENICOL
DNA-ASE
GENE REPRESSORS
PHOSPHORUS 32
TRANSCRIPTION
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
ESTERASES
HYDROLASES
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEIC ACIDS
NUCLEOPROTEINS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
SCLEROPROTEINS
STRUCTURAL CHEMICAL ANALYSIS
SYNTHESIS
550201* - Biochemistry- Tracer Techniques