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Nucleic Acids Research, 1991, Vol. 19, No. 18 4975-4982
© 1991

MOLECULAR BIOLOGY

Association of a change in chromatin structure with a tissue-specific switch in transcription start sites in the {alpha}2(I) collagen gene

Kristen M. Beck, Alfred H. Seekamp, G. Roger Askew, Zhu Mei, Catherine M. Farrell, Sandia Wang and Lewis N. Lukens*

Department of Molecular Biology and Biochemistry, Wesleyan University Middletown, CT 06459, USA

*To whom correspondence should be addressed

Received June 6, 1991. Accepted August 16, 1991.

Chick embryonic sternal chondrocytes do not synthesize {alpha}2(I) collagen until they are shifted by treatment with 5-bromo-2'-deoxyuridine (BrdUrd) to a fibroblastic phenotype, yet they transcribe this gene as rapidly as BrdUrd-treated cells. To examine further this transcription, the DNase I hypersensitive sites were mapped in the 5' region of this gene in chondrocytes, BrdUrd-treated chondrocytes, fibroblasts and three types of non-transcribing cells. A DNase I hypersensitive site at –200 bp, previously shown to be associated with the active transcription of this gene in fibroblasts, is not present in chondrocyte chromatin. The chondrocyte {alpha}2(I) gene contains, however, a novel major hypersensitive site in the DNA region corresponding to the fibroblast Intron 2, near the chondrocyte-specific transcription initiation site of this gene. This novel hypersensitive site is associated with the use of this alternate start site by chondrocytes, since it is lost when BrdUrd treatment causes these chondrocytes to switch to the initiation of transcription at the fibroblast start site. The BrdUrd-treated chondrocytes contain the same {alpha}2(I) hypersensitive sites as fibroblasts, except that fibroblasts have an additional, previously unreported, site at –1000 bp.


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