New paradigms for conserved, multifactorial, cis-acting regulation of meiotic recombination.
How do cells position the Spo11 (Rec12)-dependent initiation of meiotic recombination at hotspots? The mechanisms are poorly understood and a prevailing view is that they differ substantially between phylogenetic groups. However, recent work discovered that individual species have multiple different DNA sequence-specific, protein-DNA complexes that regulate (and are essential for the activation of) recombination hotspots. The cis-acting elements function combinatorially with documented examples of synergism, antagonism and redundancy. Furthermore, we provide evidence that all currently well-defined modules of this multifactorial, cis-acting regulation are conserved functionally between taxa whose latest common ancestor occurred more than 1 billion years ago. Functionally conserved components include the ATF/CREB-family heterodimer Atf1-Pcr1 and its CRE-like DNA site M26, the CCAAT-box-binding complex Php2-Php3-Php5 and the CCAAT-box, and the zinc-finger protein Rst2 and its Oligo-C motif. The newfound multiplicity, functional redundancy and conservation of cis-acting controls constitute a paradigm shift with broad implications. They provide compelling evidence that most meiotic recombination is, like transcription, regulated by sequence-specific protein-DNA complexes. And the new findings provide important mechanistic insight, such as a solution to the conundrum that Prdm9 is a 'master regulator' of--yet is dispensable for--hotspot activity in mammals.
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham Street (slot 516), Little Rock, AR 72205-7199, USA. wahlswaynep@uams.edu
Wayne P
WP
Wahls
Mari K
MK
Davidson
D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D008540:Meiosis / Q000235:genetics*; D059372:Nucleotide Motifs; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; D004247:DNA