Human Molecular Genetics, Vol 5, 1749-1758, Copyright © 1996 by Oxford University Press
M Speek, F Barry and WL Miller
Tenascin-X (TN-X) is an extracellular matrix protein encoded by a large
gene that overlaps the steroid 21-hydroxylase (P450c21) gene in the HLA
locus on chromosome 6p21.3. This may be the most complex locus in the human
genome identified to date, containing 13 overlapping transcription units in
160 kb of DNA. Previous studies determined the sequence of 39 TN-X exons,
encoding a 12 kb open reading frame, but the promoter(s) of the gene had
not been located. We identify the principal TN-X promoter and a previously
unknown 5' untranslated exon that lies more than 10 kb upstream from the
previously known exons. This promoter, which is substantially different
from the promoter for TN-C, initiates transcription in human fetal adrenal
and muscle, but expression in human NCI-H295 adrenocortical carcinoma cells
is initiated by two other promoters lying further upstream. One of these is
the same as the promoter for a recently identified Creb-related protein
(Creb-rp), but transcripts initiated form this promoter in human adrenal
NCI-H295 tumor cells are spliced differently from Creb- rp, and are largely
retained in the nuclei of these cells. By analogy with the other two
members of the tenascin family, TN-C and TN-R, it has been predicted that
TN-X should undergo alternate splicing in its fibronectin-like domains.
RACE cloning and RNase protection experiments reveal no such alternate
splicing. The TN-X gene appears to be unique in having both its 5' and 3'
ends buried in other genes.
ARTICLES
Alternate promoters and alternate splicing of human tenascin-X, a gene with 5' and 3' ends buried in other genes
Department of Pediatrics, University of California, San Francisco 94143- 0978, USA.
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