Histone H3 lysine 4 (H3K4) methylation in development and differentiation

Abstract

Covalent modification of histones on chromatin is a dynamic mechanism by which various nuclear processes are regulated. Methylation of histone H3 on lysine 4 (H3K4) implemented by the macromolecular complex COMPASS and its related complexes is associated with transcriptionally active regions of chromatin. Enzymes that catalyze H3K4 methylation were initially characterized genetically as regulators of Hox loci, long before their catalytic functions were recognized. Since their discovery, genetic and biochemical studies of H3K4 methylases and demethylases have provided important mechanistic insight into the role of H3K4 methylation in HOX gene regulation during development.

In situ histone landscape of nephrogenesis

“…Genome-wide analyses performed in a multitude of cell lines and tissues including kidney cell lines have demonstrated a strong correlation between the presence of H3K4me3 peaks around the transcription start sites and gene activity. 16,22,23 In contrast, H3K9me2/3 and H3K27me3 peaks decorate the promoters of repressed genes. 9,[24][25][26] We found a significant enrichment of H3K4me3 in Six2 + /Pax2 + progenitors as well as in Lhx1 + nascent nephron cells (Figs.…”

“…23 H3K4me3 is recognized by the basal transcription complex TFIID via the PHD finger of TAF3 and functions as a binding site for proteins that facilitate access by RNA Polymerase II to the DNA. 41 There are at least 6 functionally non-redundant H3K4 lysine KMT in mammals, which carry essential and conserved functions such as Hox gene regulation.…”

Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

“…There are six major histone methyltransferases that catalyze H3K4 methylation-Setd1a, Setd1b, Mll1, Mll2, Mll3, and Mll4-which are divided into three distinct groups according to their sequence similarity and complex formation: Set1a/b, Mll1/2, and Mll3/4 [20][21][22]. Previously, Mll2 was reported to be required for early embryogenesis, based on the observations of decreased H3K4me2/3 in maternal PNs concomitant with~30% reduction of major ZGA and developmental arrest mainly at 2-cell stages, when it was knocked out [23].…”

Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination

“…Histone H3 lysine 4 (H3K4) 3 methylation plays an important role in transcriptional regulation (1,2) and other cellular processes (3)(4)(5)(6)(7). H3K4 methylation occurs in three forms or degrees because the lysine ⑀-amino group can be mono-, di-, or tri-methylated (indicated as H3K4me1, H3K4me2, and H3K4me3, respectively).…”