The Identification And Function Explore Of H3K4me2Binding Protein

In eukaryotic cells, DNA is packaged with histones in the form of chromatin. Among various histone modifications identified, histone lysine methylation functions in virtually all chromatin based biological processes including transcriptional regulation and DNA damage repair. Each lysine residue can be mono-, di-, or tri-methylated. As a result, the biological effects of histone methylation are not only determined by the specific sites of methylation but also influenced by the methylation states. Mechanistically, histone methylation is believed to function at least in part as docking sites to recruit (or repel) specific chromatin-associated proteins called "reader" or "effector" proteins. The effector proteins are therefore critical for interpreting the methylation codes and thus mediate the biological effect of histone methylation. In this study, we identified two di-methylated H3K4effectors:NRDc and PAF1complex.nardilysin (NRDc), is a member of M16family metalloendopeptidases. In this study, we identified NRDc as a novel dimethyl-H3K4(H3K4me2) binding protein. Biochemical purification demonstrates that NRDc associates with the corepressor NCoR complex. We identified target genes repressed by NRDc through microarray. We showed that NRDc is physically associated with and recruits the NCoR complex to the target genes tested and this association requires its H3K4me2binding activity. Thus, our study has identified a novel H3K4me2binding protein and revealed a role of NRDc in transcriptional regulation.PAF1complex is a RNA pol â…¡ associtated elongation factor and mediates several histone modifications in gene transcription. In this study, we identified PAF1complex as H3and H3K4me2specific binding proteins. We also found the PAF1subunit of the PAF1complex is likely responsible for H3and H3K4me2. We mapped the function domain responsible for H3and H3K4me2specific binding to the Oterminus of PAF1. Our study provides evidence that PAF1complex specificly binds H3and H3K4me2through PAF1subunit.