Ky. Chau et al., A novel downstream positive regulatory element mediating transcription of the human high mobility group (HMG) I-C gene, FEBS LETTER, 457(3), 1999, pp. 429-436
The high mobility group (HMG) I proteins are small, non-histone chromosomal
proteins that promote gene activation during development and within rapidl
y dividing cells. They do so by facilitating enhanceosome formation on indu
cible genes, via both protein/DNA and protein/protein interactions. The HMG
IC gene is tightly regulated, normally being expressed exclusively during
embryonic development. However, HMG I-C expression is also observed frequen
tly in a number of tumor types, and this expression has been shown to contr
ibute to the malignant transformation process. With the aim of dissecting p
athways that lead to aberrant expression of HMG I-C in tumor cells, we have
analyzed HMG I-C gene regulation in the human hepatoma cell line PLC/PRF/5
, One of the two HMG I-C transcripts detected in this cell line originates
from a novel downstream initiation site at nucleotide -161 relative to the
first methionine, Transcription from the downstream initiation site is medi
ated by a PRE located between nt -222 and -217, We show here that the Spl a
nd Sp3 transcription factors interact with the PRE and transactivate the HM
G I-C promoter in a cooperative fashion. This study provides the first char
acterization of this downstream HMG I-C promoter. (C) 1999 Federation of Eu
ropean Biochemical Societies.