Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions
Mendenhall, Eric M.
Williamson, Kaylyn E.
Zou, James Y.
Joung, J. Keith
MetadataShow full item record
CitationMendenhall, 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.
AbstractMammalian 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406682
- HMS Scholarly Articles