Histone 3 lysine 4 methylation (H3K4me) is a highly evolutionary conserved chromatin modification associated with active transcription, and its three methylation states-mono, di, and trimethylation-mark distinct regulatory elements. However, whether H3K4me plays functional roles in transcriptional regulation or is merely a by-product of histone methyltransferases recruited to actively transcribed loci is still under debate. Here, we outline the studies that have addressed this question in yeast, Drosophila, and mammalian systems. We review evidence from histone residue mutation, histone modifier manipulation, and epigenetic editing, focusing on the relative roles of H3K4me1 and H3K4me3. We conclude that H3K4me1 and H3K4me3 may have convergent functions in establishing open chromatin and promoting transcriptional activation during cell differentiation.
Keywords: Chromatin; differentiation; histone; methylation; transcription.