Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions

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Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions

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Title: Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions
Author: Mendenhall, Eric M.; Williamson, Kaylyn E.; Reyon, Deepak; Zou, James Y.; Ram, Oren; Joung, J. Keith; Bernstein, Bradley E.

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Citation: Mendenhall, Eric M., Kaylyn E. Williamson, Deepak Reyon, James Y. Zou, Oren Ram, J. Keith Joung, and Bradley E. Bernstein. 2013. “Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions.” Nature biotechnology 31 (12): 10.1038/nbt.2701. doi:10.1038/nbt.2701. http://dx.doi.org/10.1038/nbt.2701.
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Abstract: Mammalian gene regulation is dependent on tissue-specific enhancers that can act across large distances to influence transcriptional activity1-3. Mapping experiments have identified hundreds of thousands of putative enhancers whose functionality is supported by cell type–specific chromatin signatures and striking enrichments for disease-associated sequence variants4-11. However, these studies did not address the in vivo functions of the putative elements or their chromatin states and could not determine which genes, if any, a given enhancer regulates. Here we present a strategy to investigate endogenous regulatory elements by selectively altering their chromatin state using programmable reagents. Transcription activator–like (TAL) effector repeat domains fused to the LSD1 histone demethylase efficiently remove enhancer-associated chromatin modifications from target loci, without affecting control regions. We find that inactivation of enhancer chromatin by these fusion proteins frequently causes down-regulation of proximal genes, revealing enhancer target genes. Our study demonstrates the potential of ‘epigenome editing’ tools to characterize an important class of functional genomic elements.
Published Version: doi:10.1038/nbt.2701
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858395/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406682
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