Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila

Abstract Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, development...

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Autores principales:	Nevine A. Shalaby, Raheel Sayed, Qiao Zhang, Shane Scoggin, Susan Eliazer, Adrian Rothenfluh, Michael Buszczak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/47ad0110818946e8ae66ce69c73acfe1
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spelling	oai:doaj.org-article:47ad0110818946e8ae66ce69c73acfe12021-12-02T11:53:05ZSystematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila10.1038/s41598-017-05004-w2045-2322https://doaj.org/article/47ad0110818946e8ae66ce69c73acfe12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05004-whttps://doaj.org/toc/2045-2322Abstract Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to “fine-tune” different biological processes.Nevine A. ShalabyRaheel SayedQiao ZhangShane ScogginSusan EliazerAdrian RothenfluhMichael BuszczakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nevine A. Shalaby Raheel Sayed Qiao Zhang Shane Scoggin Susan Eliazer Adrian Rothenfluh Michael Buszczak Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
description	Abstract Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to “fine-tune” different biological processes.
format	article
author	Nevine A. Shalaby Raheel Sayed Qiao Zhang Shane Scoggin Susan Eliazer Adrian Rothenfluh Michael Buszczak
author_facet	Nevine A. Shalaby Raheel Sayed Qiao Zhang Shane Scoggin Susan Eliazer Adrian Rothenfluh Michael Buszczak
author_sort	Nevine A. Shalaby
title	Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
title_short	Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
title_full	Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
title_fullStr	Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
title_full_unstemmed	Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila
title_sort	systematic discovery of genetic modulation by jumonji histone demethylases in drosophila
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/47ad0110818946e8ae66ce69c73acfe1
work_keys_str_mv	AT nevineashalaby systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT raheelsayed systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT qiaozhang systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT shanescoggin systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT susaneliazer systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT adrianrothenfluh systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila AT michaelbuszczak systematicdiscoveryofgeneticmodulationbyjumonjihistonedemethylasesindrosophila
_version_	1718394863545745408

Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila

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