title: The Tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated lysine 79 of histone H3.
abstract: Spinal muscular atrophy (SMA) is a muscular disease characterized by the death of motoneurons, and is a major genetic cause of infant mortality. Mutations in the SMN1 gene, which encodes the protein survival motor neuron (SMN), are responsible for the disease. SMN belongs to the Tudor domain protein family, whose members are known to interact with methylated arginine (R) or lysine (K) residues. SMN has well-defined roles in the metabolism of small non-coding ribonucleoproteins (snRNPs) and spliceosome activity. We previously showed that SMN relocated to damaged interphase centromeres, together with the Cajal-body-associated proteins coilin and fibrillarin, during the so-called interphase centromere damage response (iCDR). Here we reveal that SMN is a chromatin-binding protein that specifically interacts with methylated histone H3K79, a gene expression- and splicing-associated histone modification. SMN relocation to damaged centromeres requires its functional Tudor domain and activity of the H3K79 methyltransferase DOT1L. In vitro pulldown assays showed that SMN interacts with H3K79me1,2 at its functional Tudor domain. Chromatin immunoprecipitation confirmed that SMN binds to H3K79me1,2-containing chromatin in iCDR-induced cells. These data reveal a novel SMN property in the detection of specific chromatin modifications, and shed new light on the involvement of a putative epigenetic dimension to the occurrence of SMA.
authors.affiliation: Centre de Génétique et Physiologie Moléculaire et Cellulaire CNRS, UMR5534, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France.
authors.forename: Mirna
authors.initials: M
authors.lastname: Sabra
authors.forename: Pascale
authors.initials: P
authors.lastname: Texier
authors.forename: Jhony
authors.initials: J
authors.lastname: El Maalouf
authors.forename: Patrick
authors.initials: P
authors.lastname: Lomonte
mesh_terms: D002352:Carrier Proteins; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000378:metabolism; D055532:SMN Complex Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D055532:SMN Complex Proteins; C068921:p80-coilin; D008239:Lysine
keywords: Cajal bodies; Centromeres; HSV-1 ICP0 protein; Methylated H3K79; Survival motor neuron protein (SMN)