Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling

Developmental Cell
Julia Falo-SanjuanSarah J Bray

Abstract

Information from developmental signaling pathways must be accurately decoded to generate transcriptional outcomes. In the case of Notch, the intracellular domain (NICD) transduces the signal directly to the nucleus. How enhancers decipher NICD in the real time of developmental decisions is not known. Using the MS2-MCP system to visualize nascent transcripts in single cells in Drosophila embryos, we reveal how two target enhancers read Notch activity to produce synchronized and sustained profiles of transcription. By manipulating the levels of NICD and altering specific motifs within the enhancers, we uncover two key principles. First, increased NICD levels alter transcription by increasing duration rather than frequency of transcriptional bursts. Second, priming of enhancers by tissue-specific transcription factors is required for NICD to confer synchronized and sustained activity; in their absence, transcription is stochastic and bursty. The dynamic response of an individual enhancer to NICD thus differs depending on the cellular context.

References

Jul 25, 1998·Science·E M Blackwood, J T Kadonaga
Aug 17, 2002·Science·Michael B ElowitzPeter S Swain
Mar 13, 2003·Development Genes and Evolution·Véronique MorelFrançois Schweisguth
May 29, 2004·Science·Jonathan M Raser, Erin K O'Shea
Dec 20, 2005·Cell·Ido GoldingEdward C Cox
Feb 7, 2006·Developmental Cell·Stefano De RenzisEric Wieschaus
Mar 10, 2006·Nature·Mathias F WernetClaude Desplan
May 23, 2006·Current Biology : CB·Jonathan R ChubbRobert H Singer
Jun 6, 2006·Current Biology : CB·Robert P ZinzenDmitri Papatsenko
Aug 22, 2006·Nature Reviews. Molecular Cell Biology·Sarah J Bray
Dec 5, 2006·Developmental Cell·Robert P ZinzenMike Levine
Jul 1, 1987·Genetics·H Vässin, J A Campos-Ortega
Feb 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yunsun NamStephen C Blacklow
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Johannes BischofKonrad Basler
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Oct 13, 2009·Trends in Cell Biology·Daniel R LarsonDaniel Zenklusen
May 3, 2011·Nature Genetics·Lok-Hang SoIdo Golding
May 3, 2011·PLoS Biology·Claire V HarperMichael R H White
May 24, 2011·Methods in Enzymology·Daniel G Gibson
Jul 2, 2014·Cell Reports·Adrien SenecalXavier Darzacq
Jul 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jacques P BothmaMichael Levine
Nov 7, 2015·PLoS Computational Biology·Sandeep ChoubeyAlvaro Sanchez
Jun 14, 2016·Cell·Takashi FukayaMichael Levine
Jul 28, 2016·Nature Communications·Katjana TantaleEdouard Bertrand
Dec 13, 2016·PLoS Computational Biology·Jonathan DespondsAleksandra M Walczak
May 2, 2017·Current Biology : CB·Takashi FukayaMichael Levine
Oct 7, 2017·Genes & Development·Mustafa MirXavier Darzacq
Feb 6, 2018·Cell·Nagarajan NandagopalMichael B Elowitz
Feb 25, 2018·Molecular Systems Biology·Christoph FritzschStefan Legewie
Feb 27, 2018·Developmental Cell·Maria J Gomez-LamarcaSarah J Bray

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Citations

Dec 31, 2019·Development, Growth & Differentiation·Julia Falo-Sanjuan, Sarah J Bray
Jan 9, 2020·Science Signaling·Ralitsa R Madsen, Bart Vanhaesebroeck
Sep 4, 2020·Genetics·Stephen Small, David N Arnosti
Aug 6, 2019·Developmental Cell·ChangHwan LeeJudith Kimble
Jan 27, 2021·Current Opinion in Genetics & Development·Gabriel R CavalheiroEileen Em Furlong
Dec 11, 2020·ELife·Augusto BerrocalMichael B Eisen
Sep 30, 2020·Developmental Cell·Gloria R Garcia, Daniel R Larson
Mar 7, 2021·Gene Expression Patterns : GEP·Takashi Kaise, Ryoichiro Kageyama
Mar 26, 2020·Developmental Cell·David S Lorberbaum, Lori Sussel
Oct 2, 2020·Developmental Cell·Julien CharestLuisa Cochella
Dec 5, 2020·Physical Biology·Pierre-François LenneSham Tlili
Feb 4, 2021·Annual Review of Biophysics·David Sprinzak, Stephen C Blacklow
May 7, 2021·Genetics·Stephen Small, David N Arnosti
Nov 27, 2020·Current Opinion in Cell Biology·Nicholas C LammersHernan G Garcia
Jul 18, 2021·Physical Review. E·Zhenquan ZhangTianshou Zhou
Jul 22, 2021·Molecular Systems Biology·Victor L BassKathryn Miller-Jensen
Aug 17, 2021·The EMBO Journal·Ranjith ViswanathanStefano De Renzis

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Key Resources (RRID) Mentioned

BDSC_60340
BDSC_63821
BDSC_23650
BDSC_2747
BDSC_6663
BDSC_8727
BDSC_7196
BDSC_24483
BDSC_24749
Addgene_31865

Software Mentioned

sim
Matlab
peve
Mathworks
ClusterDraw2

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