eprintid: 1421793 rev_number: 27 eprint_status: archive userid: 608 dir: disk0/01/42/17/93 datestamp: 2014-03-21 21:19:16 lastmod: 2021-09-20 00:31:43 status_changed: 2014-03-21 21:19:16 type: article metadata_visibility: show item_issues_count: 0 creators_name: Corrigan, AM creators_name: Chubb, JR title: Regulation of Transcriptional Bursting by a Naturally Oscillating Signal. ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D77 note: © 2014 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. abstract: Transcription is highly stochastic, occurring in irregular bursts [1-3]. For temporal and spatial precision of gene expression, cells must somehow deal with this noisy behavior. To address how this is achieved, we investigated how transcriptional bursting is entrained by a naturally oscillating signal, by direct measurement of transcription together with signal dynamics in living cells. We identify a Dictyostelium gene showing rapid transcriptional oscillations with the same period as extracellular cAMP signaling waves. Bursting approaches antiphase to cAMP waves, with accelerating transcription cycles during differentiation. Although coupling between signal and transcription oscillations was clear at the population level, single-cell transcriptional bursts retained considerable heterogeneity, indicating that transcription is not governed solely by signaling frequency. Previous studies implied that burst heterogeneity reflects distinct chromatin states [4-6]. Here we show that heterogeneity is determined by multiple intrinsic and extrinsic cues and is maintained by a transcriptional persistence. Unusually for a persistent transcriptional behavior, the lifetime was only 20 min, with rapid randomization of transcriptional state by the response to oscillatory signaling. Linking transcription to rapid signaling oscillations allows reduction of gene expression heterogeneity by temporal averaging, providing a mechanism to generate precision in cell choices during development. date: 2014-01-20 official_url: http://dx.doi.org/10.1016/j.cub.2013.12.011 oa_status: green full_text_type: pub primo: open primo_central: open_green article_type_text: JOURNAL ARTICLE verified: verified_manual elements_source: PubMed elements_id: 922428 doi: 10.1016/j.cub.2013.12.011 pii: S0960-9822(13)01530-3 language_elements: ENG lyricists_name: Chubb, Jonathan lyricists_name: Corrigan, Adam lyricists_id: JRCHU69 lyricists_id: AMCOR50 full_text_status: public publication: Curr Biol volume: 24 number: 2 pagerange: 205-211 citation: Corrigan, AM; Chubb, JR; (2014) Regulation of Transcriptional Bursting by a Naturally Oscillating Signal. Curr Biol , 24 (2) pp. 205-211. 10.1016/j.cub.2013.12.011 <https://doi.org/10.1016/j.cub.2013.12.011>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1421793/1/1-s2.0-S0960982213015303-main.pdf