PRDM9

PRDM9 is a zinc finger protein with histone methyltransferase activity that catalyzes histone H3 lysine 4 trimethylation (H3K4me3) during meiotic prophase. This protein contains multiple domains, including a Kruppel-associated box (KRAB) domain, an SSX repression domain (SSXRD), a PRD1-BF1 and RIZ homologous region, a subclass of SET (PR/SET) domain, and a tandem array of C2H2 zinc fingers. The zinc finger array recognizes a short sequence motif, leading to local H3K4me3, and meiotic recombination hotspot activity.

PR/SET domain 9

Histone methyltransferase that sequentially mono-, di-, and tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 to produce respectively trimethylated 'Lys-4' (H3K4me3) and trimethylated 'Lys-36' (H3K36me3) histone H3 and plays a key role in meiotic prophase by determining hotspot localization thereby promoting meiotic recombination (PubMed:24634223, PubMed:24095733, PubMed:26833727, PubMed:27129774).
Can also methylate all four core histones with H3 being the best substrate and the most highly modified (PubMed:24095733, PubMed:24634223, PubMed:26833727).
Is also able, on one hand, to mono and di-methylate H4K20 and on other hand to trimethylate H3K9 with the di-methylated H3K9 as the best substrate (By similarity).
During meiotic prophase, binds specific DNA sequences through its zinc finger domains thereby determining hotspot localization where it promotes local H3K4me3 and H3K36me3 enrichment on the same nucleosomes through its histone methyltransferase activity (PubMed:26833727).
Thereby promotes double-stranded breaks (DSB) formation, at this subset of PRDM9-binding sites, that initiates meiotic recombination for the proper meiotic progression (By similarity).
During meiotic progression hotspot-bound PRDM9 interacts with several complexes; in early leptonema binds CDYL and EHMT2 followed by EWSR1 and CXXC1 by the end of leptonema. EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity).
In this way, controls the DSB repair pathway, pairing of homologous chromosomes and sex body formation (By similarity).
Moreover plays a central role in the transcriptional activation of genes during early meiotic prophase thanks to H3K4me3 and H3K36me3 enrichment that represents a specific tag for epigenetic transcriptional activation (By similarity).
In addition performs automethylation (By similarity).
Acetylation and phosphorylation of histone H3 attenuate or prevent histone H3 methylation (By similarity).

Chromatin organizationIEA:UniProtKB-KW
Double-strand break repair involved in meiotic recombinationISS:UniProtKB
Female gamete generationISS:UniProtKB
Histone H3-K36 dimethylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K36 trimethylationISS:UniProtKB
Histone H3-K4 dimethylationISS:UniProtKB
Histone H3-K4 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K4 monomethylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K4 trimethylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K9 methylationISS:UniProtKB
Homologous chromosome pairing at meiosisISS:UniProtKB
Male gamete generationISS:UniProtKB
Meiotic gene conversionManual Assertion Based On ExperimentIDA:MGI
Negative regulation of apoptotic processISS:UniProtKB
Positive regulation of fertilizationISS:UniProtKB
Positive regulation of histone H3-K36 trimethylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of histone H3-K4 trimethylationISS:UniProtKB
Positive regulation of reciprocal meiotic recombinationManual Assertion Based On ExperimentIMP:MGI
Regulation of gene expressionManual Assertion Based On ExperimentIBA:GO_Central
Regulation of transcription, DNA-templatedIEA:InterPro

Nucleus
Chromosome
Localizes in nuclei of pre-leptotene, leptotene, and early to mid-zygotene spermatocytes.

Mono-methylated; automethylated. Tri-methylated; automethylated. Mono-methylation is predominant; automethylation is lower and slower than H3 peptide methylation and is in a highest S-adenosyl-L-methionine concentration-dependent. There are two major sites for automethylation at Lys-368 and Lys-374. Lysines can be simultaneously methylated, such as Lys-368(me3)/Lys-372(me1), Lys-368(me1)/Lys-374(me1) and Lys-368(me1)/Lys-372(me1)/Lys-374(me1). Automethylation is an intramolecular (cis) process.