Developmental progress of germ cells through meiotic phases is closely tied to 
ongoing meiotic recombination. In mammals, recombination preferentially occurs 
in genomic regions known as hotspots; the protein that activates these hotspots 
is PRDM9, containing a genetically variable zinc finger (ZNF) domain and a 
PR-SET domain with histone H3K4 trimethyltransferase activity. PRDM9 is required 
for fertility in mice, but little is known about its localization and 
developmental dynamics. Application of spermatogenic stage-specific markers 
demonstrates that PRDM9 accumulates in male germ cell nuclei at pre-leptonema to 
early leptonema but is no longer detectable in nuclei by late zygonema. By the 
pachytene stage, PRDM9-dependent histone H3K4 trimethyl marks on hotspots also 
disappear. PRDM9 localizes to nuclei concurrently with the deposition of meiotic 
cohesin complexes, but is not required for incorporation of cohesin complex 
proteins into chromosomal axial elements, or accumulation of normal numbers of 
RAD51 foci on meiotic chromatin by late zygonema. Germ cells lacking PRDM9 
exhibit inefficient homology recognition and synapsis, with aberrant repair of 
meiotic DNA double-strand breaks and transcriptional abnormalities 
characteristic of meiotic silencing of unsynapsed chromatin. Together, these 
results on the developmental time course for nuclear localization of PRDM9 
establish its direct window of function and demonstrate the independence of 
chromosome axial element formation from the concurrent PRDM9-mediated activation 
of recombination hotspots.