Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing.
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.
Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.|Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
James R
JR
Davie
Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.|Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
Wayne
W
Xu
Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.|Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
Genevieve P
GP
Delcuve
D000107:Acetylation; D000818:Animals; D018899:CpG Islands; D044127:Epigenesis, Genetic; D005091:Exons; D051548:Histone Acetyltransferases / Q000378:metabolism*; D042421:Histone Code; D056466:Histone Demethylases / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007438:Introns; D008239:Lysine / Q000737:chemistry*; D008745:Methylation; D009707:Nucleosomes / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012322:RNA Precursors / Q000737:chemistry*; D012326:RNA Splicing; D014158:Transcription, Genetic
D006657:Histones; D009707:Nucleosomes; D012322:RNA Precursors; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D008239:Lysine
epigenetics; expression génique; gene expression; histone H3 lysine 4 trimethylation; pre-mRNA splicing; tri-méthylation de la lysine 4 de l’histone H3; épigénétique; épissage du pré-ARNm