title: A transcription factor-based mechanism for mouse heterochromatin formation.
abstract: Heterochromatin is important for genome integrity and stabilization of gene-expression programs. We have identified the transcription factors Pax3 and Pax9 as redundant regulators of mouse heterochromatin, as they repress RNA output from major satellite repeats by associating with DNA within pericentric heterochromatin. Simultaneous depletion of Pax3 and Pax9 resulted in dramatic derepression of major satellite transcripts, persistent impairment of heterochromatic marks and defects in chromosome segregation. Genome-wide analyses of methylated histone H3 at Lys9 showed enrichment at intergenic major satellite repeats only when these sequences retained intact binding sites for Pax and other transcription factors. Additionally, bioinformatic interrogation of all histone methyltransferase Suv39h-dependent heterochromatic repeat regions in the mouse genome revealed a high concordance with the presence of transcription factor binding sites. These data define a general model in which reiterated arrangement of transcription factor binding sites within repeat sequences is an intrinsic mechanism of the formation of heterochromatin.
authors.affiliation: Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Aydan
authors.initials: A
authors.lastname: Bulut-Karslioglu
authors.forename: Valentina
authors.initials: V
authors.lastname: Perrera
authors.forename: Manuela
authors.initials: M
authors.lastname: Scaranaro
authors.forename: Inti Alberto
authors.initials: IA
authors.lastname: de la Rosa-Velazquez
authors.forename: Suzanne
authors.initials: S
authors.lastname: van de Nobelen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Shukeir
authors.forename: Johannes
authors.initials: J
authors.lastname: Popow
authors.forename: Borbala
authors.initials: B
authors.lastname: Gerle
authors.forename: Susanne
authors.initials: S
authors.lastname: Opravil
authors.forename: Michaela
authors.initials: M
authors.lastname: Pagani
authors.forename: Simone
authors.initials: S
authors.lastname: Meidhof
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.forename: Monika
authors.initials: M
authors.lastname: Lachner
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D020090:Chromosome Segregation; D004276:DNA, Satellite / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016678:Genome; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D000072041:PAX3 Transcription Factor; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004276:DNA, Satellite; D006570:Heterochromatin; D006657:Histones; D000072041:PAX3 Transcription Factor; D051757:PAX5 Transcription Factor; D051763:PAX7 Transcription Factor; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C497282:Pax5 protein, mouse; C497322:Pax7 protein, mouse; C488759:Pax9 protein, mouse; D012097:Repressor Proteins; C068686:Pax3 protein, mouse; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D008239:Lysine