Negative Regulation of Transcription

Ericsson, J., Usheva, A. and Edwards, P.A. YYl is a negative regulator of transcription of three sterol regulatory element-binding protein-responsive genes. J Biol Chem, 274 (1999) 14508-14513. 

It should be noted that the NRE defined in these experiments is distinct from the previously described c-mos UMS sequence (Blair et al., 1984 Wood et al., 1984). The UMS is located approximately 1.4 kb upstream of the c-mos spermatocyte promoter and was identified because it blocked activation of c-mos transforming potential by insertion of retroviral promoters. It is thought to act as a transcriptional terminator, blocking transcription of c-mos initiated at upstream sequences. However, both the spermatocyte and oocyte transcription initiation sites are substantially downstream of the UMS. Moreover, the presence or absence of the UMS does not affect c-mos expression in either microin-jected oocytes (Pal et al., 1991) or transfected NIH 3T3 cells (Zinkel et al., 1992). It thus appears unlikely that the UMS functions as a negative regulator of c-mos transcription from either the spermatocyte or oocyte promoters in somatic cells. 

Overall, histone acetylation and deacetylation represents an important tool with which transcription can be positively or negatively influenced. The nucleosomes and, in a further sense, chromatin structure assiune a central role in the regulation of transcription. Nucleosome structure and nucleosome position can decisively contribute to the accessibility of DNA elements for transcription factors. The nucleosomes function as a framework that determines the spatial arrangement of a region of the DNA. Tlie nucleosome constellation must be modified during transcription initiation, whereby the post-translational modification of histones in the form of acetylation or deacetylation plays a significant role. The participation of other non-histone proteins remains an open issue and it is also imclear how a constitutive and permanent inactivation of a section of DNA can be accomplished via the chromatin structure. 

Beerli, R.R., Dreier, B. Barbas, C.F., 3rd. Positive and negative regulation of endogenous genes by designed transcription factors. Proc Natl Acad Sci USA 2000 97 1495-1500. 

K. Salnikow, S. Wang, and M. Costa, Induction of activating transcription factor 1 by nickel and its role as a negative regulator of thrombospondin I gene expression. Cancer Res. 57(22) 5060, 1997. 

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