The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA
Open accessAbstract
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA) based on global nuclear run-on sequencing (GRO-seq) analysis, with a unique class apparently requiring no nucleosome remodelling to induce specific enhancer–promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.
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Cites
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Cited by
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Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187
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Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation
Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A. Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., et al. (2013) · Nature · doi:10.1038/nature12210 · Cited by 1,049
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Metadata
- Authors
- Wang, D., Garcia-Bassets, I., Benner, C., Li, W., Su, X., Zhou, Y., Qiu, J., Liu, W., Kaikkonen, M. U., Ohgi, K. A., Glass, C. K., Rosenfeld, M. G., & Fu, X.-D.
- Venue
- Nature
- Published
- 2011-05-15
- Volume
- 474
- Issue
- 7351
- Pages
- 390-394
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1996060670
- Cited by
- 827
- References
- 10
- FWCI
- 31.86
- Type
- journal article
- Language
- en
- Open access
- green
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