title: TALE-directed local modulation of H3K9 methylation shapes exon recognition.
abstract: In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally restricted alteration of histone methylation modulates the splicing of target exons. We provide evidence that a local increase in H3K9 di- and trimethylation promotes inclusion of the target alternative exon, while demethylation by JMJD2D leads to exon skipping. We further demonstrate that H3K9me3 is localized on internal exons genome-wide suggesting a general role in splicing. Consistently, targeting of the H3K9 demethylase to a weak constitutive exon reduced co-transcriptional splicing. Together our data show H3K9 methylation within the gene body is a factor influencing recognition of both constitutive and alternative exons.
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Bieberstein
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Kozáková
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Huranová
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Prasoon K
authors.initials: PK
authors.lastname: Thakur
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Krchňáková
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Krausová
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Fernando
authors.initials: F
authors.lastname: Carrillo Oesterreich
authors.affiliation: Institute of Molecular Genetics of the ASCR, v. v. i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Staněk
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D000071336:Transcription Activator-Like Effectors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D005353:Fibronectins; D006657:Histones; D000071336:Transcription Activator-Like Effectors; D008239:Lysine