70 research outputs found
Formation of regulatory modules by local sequence duplication
Turnover of regulatory sequence and function is an important part of
molecular evolution. But what are the modes of sequence evolution leading to
rapid formation and loss of regulatory sites? Here, we show that a large
fraction of neighboring transcription factor binding sites in the fly genome
have formed from a common sequence origin by local duplications. This mode of
evolution is found to produce regulatory information: duplications can seed new
sites in the neighborhood of existing sites. Duplicate seeds evolve
subsequently by point mutations, often towards binding a different factor than
their ancestral neighbor sites. These results are based on a statistical
analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome,
and a comparison set of intergenic regulatory sequence in Saccharomyces
cerevisiae. In fly regulatory modules, pairs of binding sites show
significantly enhanced sequence similarity up to distances of about 50 bp. We
analyze these data in terms of an evolutionary model with two distinct modes of
site formation: (i) evolution from independent sequence origin and (ii)
divergent evolution following duplication of a common ancestor sequence. Our
results suggest that pervasive formation of binding sites by local sequence
duplications distinguishes the complex regulatory architecture of higher
eukaryotes from the simpler architecture of unicellular organisms
Stable growth of simian virus 40 recombinants containing multimerized enhancers.
Multiple copies of each of three genetically defined simian virus 40 protoenhancers, A, B, and C, were able to substitute for the wild-type simian virus 40 enhancer. Although the recombinant viruses grew poorly, they could be propagated without the accumulation of enhancer rearrangements that might improve viability. Mutations that inactivate the multimerized B and C protoenhancers abolished virus growth, but, unexpectedly, a mutation that inactivates the octamer-enhanson within the B protoenhancer increased virus viability. This positive effect may reflect loss of repression of the B protoenhancer by the ubiquitous octamer-motif-binding protein Oct-1
Intragenic Sequences Affect the Expression of the Gene Encoding Glial Fibrillary Acidic Protein
The Mechanism of sigma-Crystallin Gene Regulation: Cooperation of Lens-Specific and Non-Specific Elements1
A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli
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