During meiosis, homologous chromosomes must correctly identify one another in order for proper alignment, synapsis, and recombination to occur. Improper pairing between chromosomes can lead to aneuploidies causing defective gamete formation and embryonic lethality. Currently, very little is known about homologous chromosome recognition and discrimination. There has been evidence supporting the role of DNA Double Strand Breaks (DSB) and homologous recombination in homolog pairing. However, mutants lacking the ability to form DSBs in Drosophila and C. elegans can still properly align homologous chromosomes, showing that DNA DSB independent mechanisms exist. C. elegans chromosomes have pairing centers composed of DNA sequences at ends of chromosomes that are required for efficient pairing, but the sequences are not all unique to single chromsomes. Furthermore, many organisms have highly repetitive genome content, making DNA sequence risky for homology searching. What forms the basis of homolog recognition?
The specific patterns of active transcription are distinct for each chromosome during meiosis. Peter Cook has previously proposed that aspects of such transcription patterns may provide a “bar-code” for homolog recognition, possibly through shared “transcription factories”(Xu and Cook, 2008). This hypothesis, while intriguing, is fundamentally difficult to test. However, transcription through a gene also “marks” that gene with specific epigenetic modifications, such as the methylation of Lysines 4, 36, and 79 on Histone H3 (H3K4me, H3K36me, and H3K79me, respectively). Thus regions of transcription and repression create alternating patterns of chromatin modifications, unique to each chromosome, that could be recognized by specific proteins and contribute to homology recognition. Indeed, the Nabeshima lab recently showed that pairing center-independent pairing defects were observed in the germline of C.elegans mrg-1 mutants (Dombecki et al., 2011). mrg-1 encodes a chromodomain protein whose mammalian homolog, MRG15 recognizes and binds to H3K36me. We are currently examining the role of histone modifications, and their cognate binding proteins such as MRG-1, in homology recognition and discrimination during meiosis.