ZCWPW1 has co-evolved with PRDM9, in particular the PRDM9-SET domain, and although not involved in PRDM9's role in positioning recombination events, it is required for PRDM9's role in pairing chromosomes.
In humans, specific sequence features can predict whether meiotic recombination occurs at sites bound by the protein PRDM9, whose DNA-binding zinc-finger domain can unexpectedly bind to gene promoters and to other copies of PRDM9.
Biochemical and genetic approaches uncover a chromatin remodeler for PRDM9 binding and the parallel local epigenetic modification of cytosines in mouse spermatocytes.
ZCWPW1 is a histone modification reader that localizes to DMC1-labelled double-strand break hotspots in a largely PRDM9-dependent manner, where it facilitates completion of synapsis by mediating DSB repair process.
Modeling the evolution of PRDM9 in light of recent results implicating the importance of PRDM9 binding symmetry suggests the advantage of new PRMD9 alleles is in limiting the number of binding sites used effectively rather than increasing net binding.
Prdm9-generated meiotic asynapsis of homologous chromosomes in mouse subspecific hybrids causes hybrid sterility and can be reversed by introducing random stretches of consubspecific sequence (≥ 27Mb) on four chromosomes most sensitive to asynapsis.
Mohamed Mahgoub, Jacob Paiano ... Todd S Macfarlan
The meiotic recombination landscape in vertebrates was re-engineered via the co-evolution of a dual histone H3K4/H3K36 methylation 'writer' PRDM9 and its 'reader' ZCWPW1 that facilitates efficient double strand break repair.
The exogenous DNA DSBs improve meiotic chromosome pairing in mouse inter-subspecific hybrids, thus providing an evidence for a DSB-dependent mechanism of the PRDM9-controlled synapsis failure and infertility.
