A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus.

Abstract

A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus (transcription it is the strongest transcription enhancer found to date. (ii) It is an extremely long enhancer, spaing >700 base pairs. (iil) It consists of a rather complex pattern of sequence repeats, the longest of which is 181 base pairs. Also, several types of short sequence motifs are scattered throughout the enhancer in monomeric, heterodimeric, or homodimeric (palindromic) form. These motifs have been identified to be components of other enhancers and promoters, and they are presumably binding sites for specific nuclear factors. Our analysis suggests that enhancers are composed of a modular arrangement of short conserved sequence motifs and that enhancer strength is correlated with the redundancy of these motifs.

Trans-activation of the mouse cytomegalovirus immediate early gene enhancer by ras oncogenes

“…It controls the expression of IE polypeptides required for efficient activation of the promoter of the next temporal class, the early genes (Dorsch-Hasler et al, 1985;Keil et al, 1987). Therefore these proteins play a key role in the progression of the M C M V lytic cycle, and their cellular levels may be critical in determining whether MCMV replication proceeds.…”

“…The three IE genes (IE1, IE2 and IE3) are expressed in the absence of prior viral protein synthesis, and their products are directly involved in the regulation of gene expression throughout infection (Keil et al, 1987;Manning & Mocarski, 1988;Messerle et al, 1992). Transcription of IE genes is regulated by a strong viral enhancer (Dorsch-Hasler et al, 1985;G. Gribaudo & S. Landolfo, unpublished results).…”

Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

“…Their analysis reveals multiple rearrangements of the enhancer, typically duplications of some and deletions of other parts (Moens et al, 1995;Gosert et al, 2008); the most likely explanation is that the BKPyV archetypal enhancer has evolved to keep viral gene expression under careful control, such that the virus replicates just enough to be maintained within the host but remains 'under the radar' of the immune system. The longest, and also strongest, viral enhancers are found in cytomegaloviruses, large members of the herpesvirus family (Boshart et al, 1985;Dorsch-Häsler et al, 1985).…”

Adenovirus-mediated expression of an elastase-specific inhibitor (elafin): a comparison of different promoters

“…One of the objectives of this study was therefore to compare, both in vitro and in vivo, the levels of elafin secreted when under the control of the human cytomegalovirus (HCMV) promoter, a 373-bp fragment (−299 to +72 relative to transcriptional start 26 ), the adenovirus major late promoter (MLP) 27 and the mouse cytomegalovirus IE promoter (MCMV), a 1.4-kb (−1336 to +36) fragment of the pHind33 plasmid, a gift of U Koszinowski, University of Heidelberg, Germany. 28 Although the E3 deletions in pJM17 and pBHG10 are not completely identical (1.9 kb between 79.4 and 84.8 map units (mu) and 2.7 kb between 78.0 and 85.6, respectively), the outcome is similar in that it removes the major portion of all E3 messages. 29 In vitro experiments showed unambiguously that the MCMV promoter drives constitutively high levels of the elafin cDNA as assessed by mRNA and protein levels ( Figure 2 and Table 1).…”

“…The strength of this particular promoter is probably due to the presence of the strongest gene enhancer (800 bp) isolated so far. 28 The choice of a strong promoter in gene transfer experiments is particularly important in order to achieve significant expression of the protein of interest in vivo. In vivo, it is also probable that the efficacy of particular promoters will depend upon the organ to which the transfer is targeted.…”