Biology Reference
In-Depth Information
5
Promoters and
transcription factors
The eukaryotic transcriptional apparatus is much more complex than that of
prokaryotes and this complexity is bound up with the fact that many eukaryotic
genes are silenced by being tightly packed in chromatin (Zuckerkandl, 1997).
Transcriptional repression was a necessary pre-condition for the development of
large genomes since increasing gene number required gene expression to be
restricted both spatially and temporally. That nucleosomal packing and tran-
scriptional repression have, in eukaryotes, long been associated with each other is
evidenced by the discovery that the core histone fold is not confined to the his-
tones but has also turned up in a number of transcriptional coactivators and
repressors (Ouzounis and Kyrpides, 1996a). This ancient association is also evi-
dent in the High Mobility Group (HMG) superfamily (Section 5.2) which may be
divided into two distinct subfamilies comprising transcription factors and chro-
matin structure regulatory proteins, respectively.
The evolution of cellular processes probably involved several distinct stages:
metabolism and translation preceded transcription whereas transcription must
have preceded transcriptional repression by chromosomal packing at the dawn of
the eukaryotic era. Genome expansion was potentiated by chromosomal packing
whilst gene regulation became ever more complex as new transcription factors
emerged (Ouzounis and Kyrpides, 1996b). The last universal ancestor probably
possessed basic molecular components of metabolism and translation while hav-
ing a prokaryote-like genome organization together with a transcriptional system
reminiscent of the archaea.
5.1 Promoters and enhancers
The basic mechanism of transcriptional activation has been conserved across the
spectrum of eukaryotes from yeast to human (Schena, 1989). It is therefore not
surprising that two sequence elements, the TATAAA and CCAAT boxes which
serve to coordinate the basal transcriptional machinery, are found in all eukary-
otes. Indeed, these motifs occur in the promoters of a wide variety of RNA poly-
merase II-transcribed genes. Similarly, the initiator element, a functional
analogue of the TATA box, appears to be ubiquitous in eukaryotes (Liston and
Johnson, 1999). Other sequence motifs also occur, in different combinations and
