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Covalent post-translational modifications (PTMs) of proteins can regulate the structural and functional state of a protein in the absence of primary changes in the underlying sequence. Common PTMs include phosphorylation, acetylation, and methylation. Histone proteins are critical regulators of the genome and are subject to a highly abundant and diverse array of PTMs. To highlight the functional complexity added to the proteome by lysine methylation signaling, here we will focus on lysine methylation of histone proteins, an important modification in the regulation of chromatin and epigenetic processes. We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Multiple endocrine neoplasia type 1 (MEN1) is a heriditary syndrome characterised by the occurrence of parathyroid, gastroenteropancreatic and pituitary tumours. The MEN1 gene product, menin, co-activates gene transcription by recruiting histone methyltransferases for lysine 4 of histone H3 (H3K4). We investigated whether in MEN1 tumours global changes in H3K4 trimethylation (H3K4me3) occur or whether alterations in gene expression can be observed. By immunohistochemistry we found that global levels of H3K4me3 are not affected in MEN1-related parathyroid adenomas. Menin can interact directly with the vitamin D receptor (VDR) and enhance the transcriptional activity of VDR. Messenger RNA levels of VDR target genes CYP24 and KLK6 were significantly lower in MEN1 parathyroid adenomas compared to normal tissue. Thus, aberrant gene expression in MEN1 tumours is not caused by lower global H3K4me3, but rather by specific effects on genes that are regulated by menin-interacting proteins, such as VDR.

Methylation of lysine 4 on histone H3 (H3K4) at promoters is tightly linked to transcriptional regulation in human cells. At least six different COMPASS-like multisubunit (SET1/MLL) complexes that contain methyltransferase activity for H3K4 have been described, but a comprehensive and quantitative analysis of these SET1/MLL complexes is lacking. We applied label-free quantitative mass spectrometry to determine the subunit composition and stoichiometry of the human SET1/MLL complexes. We identified both known and novel, unique and shared interactors and determined their distribution and stoichiometry over the different SET1/MLL complexes. In addition to being a core COMPASS subunit, the Dpy30 protein is a genuine subunit of the NURF chromatin remodeling complex. Furthermore, we identified the Bod1 protein as a discriminator between the SET1B and SET1A complexes, and we show that the H3K36me-interactor Psip1 preferentially binds to the MLL2 complex. Finally, absolute protein quantification in crude lysates mirrors many of the observed SET1/MLL complex stoichiometries. Our findings provide a molecular framework for understanding the diversity and abundance of the different SET1/MLL complexes, which together establish the H3K4 methylation landscape in human cells. [ABSTRACT FROM AUTHOR]