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Nucleic Acids Res. 2012 Nov 1;40(20):9983-9. doi: 10.1093/nar/gks761. Epub 2012 Aug 16.

New paradigms for conserved, multifactorial, cis-acting regulation of meiotic recombination.

Author information

1
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

Abstract

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.

PMID:
22904082
PMCID:
PMC3488224
DOI:
10.1093/nar/gks761
[Indexed for MEDLINE]
Free PMC Article

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