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  A Feed-Forward Circuit Controlling Inducible NF-κB Target Gene Activation by Promoter Histone Demethylation

van Essen, D., Zhu, Y., & Saccani, S. (2010). A Feed-Forward Circuit Controlling Inducible NF-κB Target Gene Activation by Promoter Histone Demethylation. Molecular Cell, 39, 750-760.

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 Creators:
van Essen, Dominic1, Author              
Zhu, Yina1, Author              
Saccani, Simona1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Abstract: Activation of transcription from a silenced state is crucial to achieve specific gene expression in many biological contexts. Methylation of lysine 9 on histone H3 (H3K9) is widely associated with transcriptional silencing, and its disappearance is linked to the activation of several inflammatory genes by NF-κB. Here we describe that this event is controlled by a feed-forward circuit catalyzed by the activity of the histone demethylase Aof1 (also known as Lsd2/Kdm1b). We find that Aof1 is required for removal of dimethyl H3K9 at specific promoters, and thereby it controls stimulus-induced recruitment of NF-κB and gene expression. However, Aof1 is itself recruited by interaction with the c-Rel subunit of NF-κB, which is found at low levels associated with promoters in unstimulated cells. Thus, at these tightly regulated genes, NF-κB functions both as a transcriptional activator and as an upstream targeting signal that marks promoters to be derepressed by histone demethylation.

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Language(s): eng - English
 Dates: 2010-09-10
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 536157
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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: 39 Sequence Number: - Start / End Page: 750 - 760 Identifier: -