Unusual methylation pattern of the alpha 2 (l) collagen gene.

We studied the methylation pattern of the alpha 2 (type 1) collagen gene in DNA from five cell types with varying rates of type I collagen synthesis: chick embryo fibroblast (CEF), CEF transformed by Rous sarcoma virus, erythrocyte, brain and sperm. The methylation-sensitive restriction enzymes, Msp I, Hpa II, Ava I and Sma I were used to detect methylation in three regions of the alpha 2 (type I) collagen gene: a 5.7 kb region, which includes the start site of transcription and the first two exons of the collagen gene; a 5.2 kb region containing exons in the middle of the gene; and a 3.5 kb region containing exons in the 3' portion of the gene. The DNA around the start site of transcription is not methylated whether or not the cells synthesize collagen. In contrast, the DNA from the central and 3' region of the gene is methylated to about the same extent whether or not the cells make collagen. Our data indicate that a gene that is methylated can be actively transcribed and that the level of expression of the alpha 2 (type I) collagen gene seems to be independent of methylation.