A transcription factor–based mechanism for mouse heterochromatin formation
| Autor: | Thomas Manke, Valentina Perrera, Johannes Popow, Borbala Gerle, Thomas Jenuwein, Nicholas Shukeir, Susanne Opravil, Michaela Pagani, Manuela Scaranaro, Aydan Bulut-Karslioglu, Suzanne van de Nobelen, Thomas Brabletz, Simone Meidhof, Monika Lachner, Inti A. De La Rosa-Velázquez |
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| Rok vydání: | 2012 |
| Předmět: |
Euchromatin
Heterochromatin PAX5 Transcription Factor Molecular Sequence Data DNA Satellite Biology Methylation Histones Mice Structural Biology Chromosome Segregation Animals Paired Box Transcription Factors Constitutive heterochromatin PAX3 Transcription Factor Molecular Biology Pericentric heterochromatin Genetics Binding Sites Genome Base Sequence Lysine Cell Cycle EZH2 PAX7 Transcription Factor Methyltransferases Fibroblasts Mice Mutant Strains Repressor Proteins DNA binding site Heterochromatin protein 1 PAX9 Transcription Factor |
| Zdroj: | Nature Structural and Molecular Biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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