Cis -regulatory control of transcriptional timing and noise in response to estrogen.

Autor:	Ginley-Hidinger M; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA., Abewe H; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Osborne K; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Richey A; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA., Kitchen N; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Mortenson KL; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Wissink EM; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Lis J; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Zhang X; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Gertz J; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 14. Date of Electronic Publication: 2024 Feb 14.
DOI:	10.1101/2023.03.14.532457
Abstrakt:	Cis-regulatory elements control transcription levels, temporal dynamics, and cell-cell variation or transcriptional noise. However, the combination of regulatory features that control these different attributes is not fully understood. Here, we used single cell RNA-seq during an estrogen treatment time course and machine learning to identify predictors of expression timing and noise. We find that genes with multiple active enhancers exhibit faster temporal responses. We verified this finding by showing that manipulation of enhancer activity changes the temporal response of estrogen target genes. Analysis of transcriptional noise uncovered a relationship between promoter and enhancer activity, with active promoters associated with low noise and active enhancers linked to high noise. Finally, we observed that co-expression across single cells is an emergent property associated with chromatin looping, timing, and noise. Overall, our results indicate a fundamental tradeoff between a gene's ability to quickly respond to incoming signals and maintain low variation across cells.
Databáze:	MEDLINE
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