A transcription factor-based mechanism for mouse heterochromatin formation

Bulut-Karslioglu, Aydan; Perrera, Valentina; Scaranaro, Manuela; de la Rosa-Velazquez, Inti Alberto; van de Nobelen, Suzanne; Shukeir, Nicholas; Popow, Johannes; Gerle, Borbala; Opravil, Susanne; Pagani, Michaela; Meidhof, Simone; Brabletz, Thomas; Manke, Thomas; Lachner, Monika; Jenuwein, Thomas

doi:10.1038/nsmb.2382

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A transcription factor-based mechanism for mouse heterochromatin formation

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Bulut-Karslioglu, Aydan
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Perrera, Valentina
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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de la Rosa-Velazquez, Inti Alberto
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

van de Nobelen, Suzanne
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Shukeir, Nicholas
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Manke, Thomas
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lachner, Monika
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Jenuwein, Thomas
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.nature.com/articles/nsmb.2382
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Citation

Bulut-Karslioglu, A., Perrera, V., Scaranaro, M., de la Rosa-Velazquez, I. A., van de Nobelen, S., Shukeir, N., et al. (2012). A transcription factor-based mechanism for mouse heterochromatin formation. Nature Structural and Molecular Biology, 19, 1023-1030. doi:10.1038/nsmb.2382.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-8CC4-C

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.