Short sequences can efficiently recruit histone H3 lysine 27 trimethylation in the absence of enhancer activity and DNA methylation

Trimethylation of histone H3 at lysine 27 (H3K27me3) is a chromatin mark associated with Polycomb-mediated gene repression. Despite its critical role in development, it remains largely unclear how this mark is targeted to defined loci in mammalian cells. Here, we use iterative genome editing to iden...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-08, Vol.111 (33), p.E3415-E3421
Main Authors: Jermann, Philip, Hoerner, Leslie, Burger, Lukas, Schübeler, Dirk
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biological Sciences
Cell Line, Tumor
Chromatin
DNA Methylation
Enhancer Elements, Genetic
Gene expression
Histones - chemistry
Histones - metabolism
Lysine - chemistry
Mice
PNAS Plus
Transcription, Genetic
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Summary:Trimethylation of histone H3 at lysine 27 (H3K27me3) is a chromatin mark associated with Polycomb-mediated gene repression. Despite its critical role in development, it remains largely unclear how this mark is targeted to defined loci in mammalian cells. Here, we use iterative genome editing to identify small DNA sequences capable of autonomously recruiting Polycomb. We inserted 28 DNA elements at a defined chromosomal position in mouse embryonic stem cells and assessed their ability to promote H3K27me3 deposition. Combined with deletion analysis, we identified DNA elements as short as 220 nucleotides that correctly recapitulate endogenous H3K27me3 patterns. Functional Polycomb recruiter sequences are invariably CpG-rich but require protection against DNA methylation. Alternatively, their activity can be blocked by placement of an active promoter-enhancer pair in cis . Taken together, these data support the model whereby PRC2 recruitment at specific targets in mammals is positively regulated by local CpG density yet obstructed by transcriptional activity or DNA methylation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1400672111