Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.

Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monom...

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Autores principales:	Yi Kuang, Anna Pyo, Natanel Eafergan, Brittany Cain, Lisa M Gutzwiller, Ofri Axelrod, Ellen K Gagliani, Matthew T Weirauch, Raphael Kopan, Rhett A Kovall, David Sprinzak, Brian Gebelein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/46e826c091ea4d9db920f08826b85963
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spelling	oai:doaj.org-article:46e826c091ea4d9db920f08826b859632021-12-02T20:03:02ZEnhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.1553-73901553-740410.1371/journal.pgen.1009039https://doaj.org/article/46e826c091ea4d9db920f08826b859632021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009039https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monomeric CSL sites and cooperative dimer sites called Su(H) paired sites (SPS). Intriguingly, the CSL TF can also bind co-repressors to negatively regulate transcription via these same sites. Here, we tested how synthetic enhancers with monomeric CSL sites versus dimeric SPSs bind Drosophila Su(H) complexes in vitro and mediate transcriptional outcomes in vivo. Our findings reveal that while the Su(H)/Hairless co-repressor complex similarly binds SPS and CSL sites in an additive manner, the Notch activation complex binds SPSs, but not CSL sites, in a cooperative manner. Moreover, transgenic reporters with SPSs mediate stronger, more consistent transcription and are more resistant to increased Hairless co-repressor expression compared to reporters with the same number of CSL sites. These findings support a model in which SPS containing enhancers preferentially recruit cooperative Notch activation complexes over Hairless repression complexes to ensure consistent target gene activation.Yi KuangAnna PyoNatanel EaferganBrittany CainLisa M GutzwillerOfri AxelrodEllen K GaglianiMatthew T WeirauchRaphael KopanRhett A KovallDavid SprinzakBrian GebeleinPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009039 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Yi Kuang Anna Pyo Natanel Eafergan Brittany Cain Lisa M Gutzwiller Ofri Axelrod Ellen K Gagliani Matthew T Weirauch Raphael Kopan Rhett A Kovall David Sprinzak Brian Gebelein Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
description	Notch signaling controls many developmental processes by regulating gene expression. Notch-dependent enhancers recruit activation complexes consisting of the Notch intracellular domain, the Cbf/Su(H)/Lag1 (CSL) transcription factor (TF), and the Mastermind co-factor via two types of DNA sites: monomeric CSL sites and cooperative dimer sites called Su(H) paired sites (SPS). Intriguingly, the CSL TF can also bind co-repressors to negatively regulate transcription via these same sites. Here, we tested how synthetic enhancers with monomeric CSL sites versus dimeric SPSs bind Drosophila Su(H) complexes in vitro and mediate transcriptional outcomes in vivo. Our findings reveal that while the Su(H)/Hairless co-repressor complex similarly binds SPS and CSL sites in an additive manner, the Notch activation complex binds SPSs, but not CSL sites, in a cooperative manner. Moreover, transgenic reporters with SPSs mediate stronger, more consistent transcription and are more resistant to increased Hairless co-repressor expression compared to reporters with the same number of CSL sites. These findings support a model in which SPS containing enhancers preferentially recruit cooperative Notch activation complexes over Hairless repression complexes to ensure consistent target gene activation.
format	article
author	Yi Kuang Anna Pyo Natanel Eafergan Brittany Cain Lisa M Gutzwiller Ofri Axelrod Ellen K Gagliani Matthew T Weirauch Raphael Kopan Rhett A Kovall David Sprinzak Brian Gebelein
author_facet	Yi Kuang Anna Pyo Natanel Eafergan Brittany Cain Lisa M Gutzwiller Ofri Axelrod Ellen K Gagliani Matthew T Weirauch Raphael Kopan Rhett A Kovall David Sprinzak Brian Gebelein
author_sort	Yi Kuang
title	Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
title_short	Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
title_full	Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
title_fullStr	Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
title_full_unstemmed	Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.
title_sort	enhancers with cooperative notch binding sites are more resistant to regulation by the hairless co-repressor.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/46e826c091ea4d9db920f08826b85963
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Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.

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