The human genome contains a family of endogenous retroviruses, HERV-K(HML-4
), that comprises the full-length provirus HERV-K-T47D, five related elemen
ts, and hundreds of solitary long terminal repeats (LTRs). We here show tha
t HERV-K-T47D-related LTRs are dispersed over all human chromosomes and hav
e arisen after the divergence of Old and New World monkeys. By screening a
cDNA library derived from the human mammary carcinoma cell line T47D with a
HERV-K-T47D LTR probe, we isolated several clones containing LTR/cellular
gene chimeras and assessed the transcriptional activity of these LTRs in tr
ansient transfection experiments. All LTRs were able to drive the expressio
n of a reporter gene, thereby displaying distinct activities in different c
ell lines. We found that sequences located downstream of the LTR-U3 region
modulate the level of gene expression. Based on the impact of the R region
we distinguished between three different LTR types; the activity of type I
LTRs was enhanced in the presence of the LTR-R region in all call lines tes
ted, whereas a type II LTR was downregulated. Type III LTRs are characteriz
ed by lacking or having a varying influence of the R region that was depend
ent on the cell line used. Finally, our results attribute to LTR-U5-gag seq
uences a role in determining LTR activity, (C) 2001 academic Press.