title: Alternative splicing regulates the expression of G9A and SUV39H2 methyltransferases, and dramatically changes SUV39H2 functions.
abstract: Alternative splicing is the main source of proteome diversity. Here, we have investigated how alternative splicing affects the function of two human histone methyltransferases (HMTase): G9A and SUV39H2. We show that exon 10 in G9A and exon 3 in SUV39H2 are alternatively included in a variety of tissues and cell lines, as well as in a different species. The production of these variants is likely tightly regulated because both constitutive and alternative splicing factors control their splicing profiles. Based on this evidence, we have assessed the link between the inclusion of these exons and the activity of both enzymes. We document that these HMTase genes yield several protein isoforms, which are likely issued from alternative splicing regulation. We demonstrate that inclusion of SUV39H2 exon 3 is a determinant of the stability, the sub-nuclear localization, and the HMTase activity. Genome-wide expression analysis further revealed that alternative inclusion of SUV39H2 exon 3 differentially modulates the expression of target genes. Our data also suggest that a variant of G9A may display a function that is independent of H3K9 methylation. Our work emphasizes that expression and function of genes are not collinear; therefore alternative splicing must be taken into account in any functional study.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 6, IFD, 4 Place Jussieu, 75252 PARIS cedex 05, France Institut Pasteur, Département de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, 25 rue du Docteur Roux, Paris, 75015, France.
authors.forename: Oriane
authors.initials: O
authors.lastname: Mauger
authors.affiliation: Laboratory of Functional Genomics of the Université de Sherbrooke, Sherbrooke, Québec, J1E 4K8, Canada.
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.affiliation: Laboratory of Functional Genomics of the Université de Sherbrooke, Sherbrooke, Québec, J1E 4K8, Canada Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke. Québec, J1E 4K8, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.affiliation: Institut Pasteur, Département de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, 25 rue du Docteur Roux, Paris, 75015, France muchardt@pasteur.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
authors.affiliation: Institut Pasteur, Département de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, 25 rue du Docteur Roux, Paris, 75015, France allemand.eric@gmail.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Allemand
authors.affiliation: Institut Pasteur, Département de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, 25 rue du Docteur Roux, Paris, 75015, France batsche@pasteur.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Batsché
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans
chemical_list: D015254:DNA Modification Methylases