Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations

Autores
Lengyel, Iván Miguel; Soroldoni, Daniele; Oates, Andrew C.; Morelli, Luis Guillermo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.
Fil: Lengyel, Iván Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Soroldoni, Daniele. University College London; Estados Unidos
Fil: Oates, Andrew C.. University College London; Estados Unidos
Fil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Materia
NEGATIVE FEEDBACK
GENETIC OSCILLATIONS
NONLINEAR DYNAMICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18277
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillationsLengyel, Iván MiguelSoroldoni, DanieleOates, Andrew C.Morelli, Luis GuillermoNEGATIVE FEEDBACKGENETIC OSCILLATIONSNONLINEAR DYNAMICShttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.Fil: Lengyel, Iván Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Soroldoni, Daniele. University College London; Estados UnidosFil: Oates, Andrew C.. University College London; Estados UnidosFil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaInstituto de Física de Líquidos y Sistemas Biológicos2014-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18277Lengyel, Iván Miguel; Soroldoni, Daniele; Oates, Andrew C.; Morelli, Luis Guillermo; Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations; Instituto de Física de Líquidos y Sistemas Biológicos; Papers in Physics; 6; 12-2014; 1-11; 0600121852-4249CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4279/PIP.060012info:eu-repo/semantics/altIdentifier/url/http://papersinphysics.org/index.php/papersinphysics/article/view/206info:eu-repo/semantics/altIdentifier/url/http://ref.scielo.org/v88h85info:eu-repo/semantics/altIdentifier/url/https://arxiv.org/abs/1501.04040info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:31:49Zoai:ri.conicet.gov.ar:11336/18277instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:31:49.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
spellingShingle Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
Lengyel, Iván Miguel
NEGATIVE FEEDBACK
GENETIC OSCILLATIONS
NONLINEAR DYNAMICS
title_short Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_full Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_fullStr Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_full_unstemmed Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
title_sort Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations
dc.creator.none.fl_str_mv Lengyel, Iván Miguel
Soroldoni, Daniele
Oates, Andrew C.
Morelli, Luis Guillermo
author Lengyel, Iván Miguel
author_facet Lengyel, Iván Miguel
Soroldoni, Daniele
Oates, Andrew C.
Morelli, Luis Guillermo
author_role author
author2 Soroldoni, Daniele
Oates, Andrew C.
Morelli, Luis Guillermo
author2_role author
author
author
dc.subject.none.fl_str_mv NEGATIVE FEEDBACK
GENETIC OSCILLATIONS
NONLINEAR DYNAMICS
topic NEGATIVE FEEDBACK
GENETIC OSCILLATIONS
NONLINEAR DYNAMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.
Fil: Lengyel, Iván Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
Fil: Soroldoni, Daniele. University College London; Estados Unidos
Fil: Oates, Andrew C.. University College London; Estados Unidos
Fil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina
description We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/18277
Lengyel, Iván Miguel; Soroldoni, Daniele; Oates, Andrew C.; Morelli, Luis Guillermo; Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations; Instituto de Física de Líquidos y Sistemas Biológicos; Papers in Physics; 6; 12-2014; 1-11; 060012
1852-4249
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18277
identifier_str_mv Lengyel, Iván Miguel; Soroldoni, Daniele; Oates, Andrew C.; Morelli, Luis Guillermo; Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations; Instituto de Física de Líquidos y Sistemas Biológicos; Papers in Physics; 6; 12-2014; 1-11; 060012
1852-4249
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4279/PIP.060012
info:eu-repo/semantics/altIdentifier/url/http://papersinphysics.org/index.php/papersinphysics/article/view/206
info:eu-repo/semantics/altIdentifier/url/http://ref.scielo.org/v88h85
info:eu-repo/semantics/altIdentifier/url/https://arxiv.org/abs/1501.04040
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Instituto de Física de Líquidos y Sistemas Biológicos
publisher.none.fl_str_mv Instituto de Física de Líquidos y Sistemas Biológicos
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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