Transcription enhancers

Norris J, Fan D, Aleman C et al. Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J Biol Chem 1995 270[39] 22777-22782. 

Meyer, B., et. al., Hepatitis B virus X-associate protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity, Mol. Cell. Biol., 18, 978, 1998. 

The C-terminal domain of HMGN was required for transcriptional enhancement in both SV40 minichromosomes and in minichromosomes assembled using... 

HMGN proteins are thus able to decompact chromatin and activate transcription from chromatin templates. Both activities are dependent on the C-terminal domain, and it is likely that the transcriptional enhancement is a direct result of the ability of these proteins to unfold chromatin. 

Yoshinaga, S.K., Peterson, C.L., Herskowitz, I., and Yamamoto, K.R. (1992) Roles of SWIl, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science 258, 1598-1604. 

Peterson, C.L., Dingwall, A., and Scott, M.P. (1994) Five SWI/SNF subunits are components of a large multisubunit complex required for transcriptional enhancement. Proc. Natl. Acad. Sci. USA 91, 2905-2908. 

Hamamoto, FI., Hasegawa, K., Nakaune, R., Lee, Y. J., Makizumi, Y., Akutsu, K., and Flibi, T. (2001). Tandem repeat of a transcriptional enhancer upstream of the sterol 14a-demethy-lase gene (CYP51) in Penicillium digitatum. Appl. Environ. Microbiol. 66, 3421-3426. 

The binding of the ligand to the DNA-bound receptor reverses the repression and leads to an active transcriptional enhancement. One model assumes that the hormone induces dissociation of the repressing proteins so that interactions with the co-activa-tors can occur. This leads to stimulation of transcription initiation. 

The binding is with regulatory elements or enhancer/promoter regions of the gene and involves XREs or drug responsive elements (DRES). These are positive control elements or transcriptional enhancers, which function like switches. They are about 1 kilobase upstream of the CYP1A1 gene, which is part of the polycyclic hydrocarbon responsive transcriptional enhancer. 

Kustu, S., A. K. North, and D. S. Weiss, Prokaryotic transcriptional enhancers and enhancer-binding proteins. Trends Biochem. Sci. 16 397-401, 1991. First discovered in eukaryotes, enhancers have now been found to exist for a number of prokaryotic genes. 

Observations that the 5 end of the mutation domain is near the transcriptional promoter stimulated speculation that the initiation of transcription is in some way involved in the generation of mutations. Betz et al. (1994) showed that the two transcriptional enhancer elements in the K locus, one in the JC intron and the other 9 kb 3 to CK, are important for effective hypermutation. The intron enhancer appeared to be absolutely required, whereas deletion of the 3 enhancer reduced but did not abolish mutation. The promoter 5 of the VK transcription start site (Falkner and Zachau, 1984 Parslow et al., 1984) was replaced by the human P-globin promoter without deleterious effect on mutation, indicating that specific promoter elements may not be required. Heavy chain transgenes with a heterologous promoter can also undergo mutation (Tumas-Brundage and Manser, 1997). 

Figure 9.9 Interaction of the Ah-receptor-ligand complex with the 5 flanking region of the P450 1A1 gene. Two dioxin responsive elements (DREs) appear to lie approximately 1000 or more base pairs upstream from the 1A1 transcriptional s tart site. These elements appear to be transcriptional enhancers, whereas less direct evidence indicates an inhibitory element ( negative control element ) between 400 and 800 bases upstream. The negative control element may inhibit the 1A1 promoted although the conditions for this inhibition are, as yet, undefined. (Adapted from A. B. Okey, Pharmacol. Ther. 45 241-298, 1990.)...

Using highly purified receptor preparations, a series of specific receptor binding sequences have been characterized in this way. They may be located at very different distances upstream of the start site of transcription or within the gene and at either orientation thus resembling transcriptional enhancer elements. They may bind... 

Scafe, C., Chao, D., Lopes, J., Hirsch, J.R, Henry, S., and Young, R.A., 1990a, RNA polymerase II C-terminal repeat influences response to transcriptional enhancer signals. Nature 347 491-194. 

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