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  Evidence for additive and synergistic action of mammalian enhancers during cell fate determination

Choi, J., Lysakovskai, K., Lysakovskaia, K., Stik, G., Demel, C., Söding, J., et al. (2021). Evidence for additive and synergistic action of mammalian enhancers during cell fate determination. eLife, 10: e65381. doi:10.7554/eLife.65381.sa2.

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 Creators:
Choi, J.1, Author              
Lysakovskai, Kseniia, Author
Lysakovskaia, K.1, Author              
Stik, G., Author
Demel, C.1, Author              
Söding, J.2, Author              
Tian, T. V., Author
Graf, T., Author
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              
2Research Group of Computational Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1933286              

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Free keywords: transdifferentiation, transcriptional regulation, enhancer cooperation, c/ebpa
 Abstract: Enhancer activity drives cell differentiation and cell fate determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human leukemia B-cells to macrophages. Putative enhancers are established by binding of the pioneer factor C/EBPα followed by chromatin opening and enhancer RNA (eRNA) synthesis from H3K4-monomethylated regions. Using eRNA synthesis as a proxy for enhancer activity, we find that most putative enhancers cooperate in an additive way to regulate transcription of assigned target genes. However, transcription from 136 target genes depends exponentially on the summed activity of its putative paired enhancers, indicating that these enhancers cooperate synergistically. The target genes are cell type-specific, suggesting that enhancer synergy can contribute to cell fate determination. Enhancer synergy appears to depend on cell type-specific transcription factors, and such interacting enhancers are not predicted from occupancy or accessibility data that are used to detect superenhancers.

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Language(s): eng - English
 Dates: 2021-03-26
 Publication Status: Published online
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.65381.sa2
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Title: eLife
Source Genre: Journal
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Pages: - Volume / Issue: 10 Sequence Number: e65381 Start / End Page: - Identifier: -