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  PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation

Feng, W., Yonezawa, M., Ye, J., Jenuwein, T., & Grummt, I. (2010). PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. Nature Structural & Molecular Biology, 17, 445-450.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8E95-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8E96-8
Genre: Journal Article

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 Creators:
Feng, Weijun, Author
Yonezawa, Masato, Author
Ye, Jing, Author
Jenuwein, Thomas1, Author              
Grummt, Ingrid, Author
Affiliations:
1Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 Abstract: Histone lysine methylation is dynamically regulated by lysine methyltransferases and lysine demethylases. Here we show that PHD finger protein 8 (PHF8), a protein containing a PHD finger and a Jumonji C (JmjC) domain, is associated with hypomethylated rRNA genes (rDNA). PHF8 interacts with the RNA polymerase I transcription machinery and with WD repeat-containing protein 5 (WDR5)-containing H3K4 methyltransferase complexes. PHF8 exerts a positive effect on rDNA transcription, with transcriptional activation requiring both the JmjC domain and the PHD finger. PHF8 demethylates H3K9me1/2, and its catalytic activity is stimulated by adjacent H3K4me3. A point mutation within the JmjC domain that is linked to mental retardation with cleft lip and palate (XLMR-CL/P) abolishes demethylase activity and transcriptional activation. Though further work is needed to unravel the contribution of PHF8 activity to mental retardation and cleft lip/palate, our results reveal a functional interplay between H3K4 methylation and H3K9me1/2 demethylation, linking dynamic histone methylation to rDNA transcription and neural disease.

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Language(s): eng - English
 Dates: 2010-04
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 528782
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Title: Nature Structural & Molecular Biology
  Alternative Title : Nat. Struct. Mol. Biol.
Source Genre: Journal
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Pages: - Volume / Issue: 17 Sequence Number: - Start / End Page: 445 - 450 Identifier: -