A transcription factor-based mechanism for mouse heterochromatin formation

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

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A transcription factor-based mechanism for mouse heterochromatin formation

Bulut-Karslioglu, A., Perrera, V., Scaranaro, M., de la Rosa-Velazquez, I. A., van de Nobelin, S., Shukeir, N., et al. (2012). A transcription factor-based mechanism for mouse heterochromatin formation. Nature Structural & Molecular Biology, 19, 1023-1030.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-8CC4-C Version Permalink: https://hdl.handle.net/11858/00-001M-0000-002B-8CC8-4

Genre: Journal Article

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Creators:
Bulut-Karslioglu, Aydan¹, Author
Perrera, Valentina², Author
Scaranaro, Manuela, Author
de la Rosa-Velazquez, Inti Alberto², Author
van de Nobelin, Suzanne¹, Author
Shukeir, Nicholas¹, Author
Popow, Johannes, Author
Gerle, Borbala, Author
Opravil, Susanne, Author
Pagani, Michaela, Author
Meidhof, Simone, Author
Brabletz, Thomas, Author
Manke, Thomas², Author
Lachner, Monika¹, Author
Jenuwein, Thomas², Author

Affiliations:
1Max Planck Society, ou_persistent13
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644

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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.

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Language(s): eng - English

Dates: Date issued: 2012-10

Publication Status: Issued

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Rev. Type: Peer

Identifiers: eDoc: 634065

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Title: Nature Structural & Molecular Biology

Source Genre: Journal

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Pages: - Volume / Issue: 19 Sequence Number: - Start / End Page: 1023 - 1030 Identifier: -