Deciphering Histone Code Enigmas Sheds New Light on Cardiac Regeneration

Histone methylation is tightly regulated by the equilibrium between histone methyltransferases and demethylases.1 Methylation occurs on lysine (K), arginine (R), and histidine (H) residues, without affecting histone charge. Interestingly, histone methylation plays different roles in consequence of the specific position of the methylated residue. The transcribed chromatin might, in fact, be enriched in methylation at histone 3 (H3) residues K4 (H3K4), K36 (H3K36), and K79 (H3K79), whereas methylation at K9 (H3K9), K27 (H3K27), and histone 4 (H4) K20 (H4K20) characterizes silenced chromatin regions.2 The level of K methylation, such as mono-, di-, or trimethylation, is also important allowing for chromatin accessibility by transcription complexes. For example, monomethylation of H3K9 (H3K9me1) or H3K27 (H3K27me1) associates with active transcription, whereas their trimethylated forms (H3K9me3; H3Kme3) with silencing.2 Histone methyltransferases belong to the larger lysine methyltransferases family whose members incorporate the conserved methyltransferase domain first identified as part of the Su(var)3 to 9, Enhancer-of-zeste, Trithorax (SET) proteins. On the contrary, histone demethylases are included into the lysine demethylases (KDMs) and grouped into 2 major classes: the Flavin adenine dinucleotide–dependent demethylases acting on mono- and di-methylated Ks and the Jumonji demethylases, depending on Fe(II) and α-ketoglutarate cofactors, selective for trimethylated Ks1. Article, see p 1403 Among epigenetic writers, the lysine methyltransferase polycomb repressive complexes 1 and 2 (PRC1 and PRC2) gained considerable popularity in the field for their involvement in the regulation of stem cell pluripotency, embryonal development, and cancer.3 Recently, the interest of epigeneticists toward Polycomb has been further raised by the evidence that these complexes associate with many long noncoding RNAs being possibly implicated in gene regulation.4 PRC1 and PRC2 are multiprotein complexes grouped under the definition of Polycomb Group responsible for histone PTMs able to condensate …