Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I.

Abstract:

:We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T-lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expression of Ets1 with reporter plasmids containing ERR-1 or ERR-2 upstream of a basal promoter resulted in an increase in transcriptional activity. By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region. By DNase I footprint, gel mobility shift, and methylation interference analyses, ERR-1 was found to contain two Ets1 binding sites, ERE-A and ERE-B. A recombinant Ets1 protein was found to bind with higher affinity to ERE-A than to ERE-B. Binding of Ets1 to these sites appears to result in a specific and sequential protection of a 37-nucleotide sequence of the HTLV-I LTR from -154 to -118. In view of the high-level expression of Ets1 in lymphoid cells, the c-ets proto-oncogenes encode transcription factors which could play an important role in both basal and Tax1-mediated HTLV-I transcription.

journal_name

J Virol

journal_title

Journal of virology

authors

Gitlin SD,Bosselut R,Gégonne A,Ghysdael J,Brady JN

doi

10.1128/JVI.65.10.5513-5523.1991

subject

Has Abstract

pub_date

1991-10-01 00:00:00

pages

5513-23

issue

10

eissn

0022-538X

issn

1098-5514

journal_volume

65

pub_type

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