Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing

Abstract

Histone H3 lysine 4 trimethylation (H3K4me3) is often stated as a mark of transcriptionally active promoters. However, closer study of the positioning of H3K4me3 shows the mark locating primarily after the first exon at the 5' splice site and overlapping with a CpG island in mammalian cells. There are several enzyme complexes that are involved in the placement of the H3K4me3 mark, including multiple protein complexes containing SETD1A, SETD1B, and MLL1 enzymes (writers). CXXC1, which is associated with SETD1A and SETD1B, target these enzymes to unmethylated CpG islands. Lysine demethylases (KDM5 family members, erasers) demethylate H3K4me3. The H3K4me3 mark is recognized by several proteins (readers), including lysine acetyltransferase complexes, chromatin remodelers, and RNA bound proteins involved in pre-mRNA splicing. Interestingly, attenuation of H3K4me3 impacts pre-mRNA splicing, and inhibition of pre-mRNA splicing attenuates H3K4me3.

PHF13: A new player involved in RNA polymerase II transcriptional regulation and co-transcriptional splicing

“…(5) H3K4me3 and pre-mRNA splicing are interdependent as attenuation of one negatively impacts the other. 35,36,39 Together, these findings support that H3K4me3 is more relevant for co-transcriptional splicing than transcription itself. Intriguingly, CHD1, an H3K4me3 reader and chromatin remodeler was demonstrated to bridge H3K4me3 to the U2 snRNP and depletion of either CHD1 or H3K4me3, perturbed pre-mRNA splicing.…”

The florigen interactor BdES43 represses flowering in the model temperate grass Brachypodium distachyon

“…Moreover, BdES43 ‐OE resulted in late flowering and a dwarf stature under inductive LD conditions (Figure f). H3K4me3 is also known to be associated with transcriptional regulation and AS (Spies et al , ; Tian et al , ; Ding et al , ; Huang et al , ; Davie et al , ). Thus, these data suggest that the BdFTL2 regulation of BdFTL1 may be mediated by interactions with the BdES43‐H3K4me3 complex.…”

“…Considerable evidence has revealed that transcription elongation rates are tightly related to chromatin structure and directly involved in the AS events in co‐transcriptional splicing processes (Shukla and Oberdoerffer, ; Braunschweig et al , ; Kornblihtt et al , ; Bentley, ). Moreover, it is well known that H3K4 methylation exerts a significant influence on gene transcription and AS (Burnette et al , ; Spies et al , ; Tian et al , ; Ding et al , ; Huang et al , ; Ong‐Abdullah et al , ; Davie et al , ). Here we present a model for BdFTL2 regulation of BdFTL1 based on our experimental evidence and above reasoning (Figure a).…”

Wnt/β‐catenin signaling enhances transcription of the CX43 gene in murine Sertoli cells

“…As shown in Figure 3 the TBE sites located downstream the TSS exhibited higher enrichment (four-fold) of the H3K4me3 mark ( Figure 3A), which is consistent with the known role of this histone mark at the proximal promoter region of genes that are active or poised for expression. 39 However, H3K4me3 enrichment was not increased along the promoter after stimulation of the Wnt pathway ( Figure 3A). On the other hand, H3K9ac was found enriched throughout the CX43 promoter ( Figure 3B), and this enrichment resulted increased (about two-fold) after treatment of these cells with BIO, particularly within the region bearing TBE sites 3 and 4 ( Figure 3B).…”