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Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

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Science  12 Feb 2015:
1259418
DOI: 10.1126/science.1259418

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Abstract

While it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then mRNAs encoding transcription factors dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously over-represented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

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