A transcription factor-based mechanism for mouse heterochromatin formation.
Nat Struct Mol Biol, 2012/10;19(10):1023-30.
Bulut-Karslioglu A[1], Perrera V, Scaranaro M, de la Rosa-Velazquez IA, van de Nobelen S, Shukeir N, Popow J, Gerle B, Opravil S, Pagani M, Meidhof S, Brabletz T, Manke T, Lachner M, Jenuwein T
Affiliations
PMID: 22983563DOI: 10.1038/nsmb.2382
Impact factor: 18.361
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.
MeSH terms
Animals; Base Sequence; Binding Sites; Cell Cycle; Chromosome Segregation; DNA, Satellite; Fibroblasts; Genome; Heterochromatin; Histones; Lysine; Methylation; Methyltransferases; Mice; Mice, Mutant Strains; Molecular Sequence Data; PAX3 Transcription Factor; PAX5 Transcription Factor; PAX7 Transcription Factor; PAX9 Transcription Factor; Paired Box Transcription Factors; Repressor Proteins
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