Box 3.

The CFP1 protein, a conserved member of the SETD1A complex, binds to the chromatin at non-methylated CpG islands [63]. In mouse oocytes, deletion of the CFP1, leads to failure in bivalent metaphase II spindle assembly, which suggests that CFP1 may regulate α-tubulin polymerization in oocytes [134]. H3K4 trimethylation regulation via CFP1 makes the chromatin accessible to transcriptional machinery ensuring timely transcription during oocyte formation [134]. In yeast, Mad2, a spindle assembly check point (SAC) component, binds to the methylated H3K4 and regulates deactivation of the spindle assembly checkpoint [133]. Loss of Set1 or the G951S mutation, which abrogates the ability of Set1 to methylate histone H3K4, shows benomyl resistance phenotype [133]. Benomyl resistance phenotype is characterized by enhanced microtubule stability or enhanced spindle formation as cells continue to grow in the presence of benomyl (which interfere with the mitotic spindle assembly by depolymerizing microtubules and negatively affects the mitotic progression) [105]. Abrogation of H3K4 methylation also gives rise to benomyl resistance and thick mitotic spindle phenotype. Mad2 HORMA domain was revealed as conformation specific reader of H3K4me [133]. Concurring with this study, another group also implicates loss of Set1, and in turn defective methylation of H3K4 in benomyl resistance phenotype in yeast. ΔSet1 mutants show abnormal gene expression during G1/S, accompanied with deferred S-phase entry and mimic benomyl resistance. They suggest that Set1 and H3K4 methylation work in conjunction to regulate the cell-cycle progression and chromosome segregation during mitosis [105]