Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>

ABSTRACT Balancing gene expression is a fundamental challenge of all cell types. To properly regulate transcription on a genome-wide level, there are myriad mechanisms employed by the cell. One layer to this regulation is through spatial positioning, with particular chromosomal loci exerting an infl...

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Autores principales:	Alanna Cera, Maria K. Holganza, Ahmad Abu Hardan, Irvin Gamarra, Reem S. Eldabagh, Megan Deschaine, Sarah Elkamhawy, Exequiel M. Sisso, Jonathan J. Foley, James T. Arnone
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	coregulation genomics Saccharomyces cerevisiae gene expression Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2536c64f8c9c40fbba13a216b00ba416
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spelling	oai:doaj.org-article:2536c64f8c9c40fbba13a216b00ba4162021-11-15T15:22:22ZFunctionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>10.1128/mSphere.00063-192379-5042https://doaj.org/article/2536c64f8c9c40fbba13a216b00ba4162019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00063-19https://doaj.org/toc/2379-5042ABSTRACT Balancing gene expression is a fundamental challenge of all cell types. To properly regulate transcription on a genome-wide level, there are myriad mechanisms employed by the cell. One layer to this regulation is through spatial positioning, with particular chromosomal loci exerting an influence on transcription throughout a region. Many coregulated gene families utilize spatial positioning to coordinate transcription, with functionally related genes clustering together which can allow coordinated expression via adjacent gene coregulation. The mechanisms underlying this process have not been elucidated, though there are many coregulated gene families that exhibit this genomic distribution. In the present study, we tested for a role for the enhancer-promoter (EP) hypothesis, which demonstrates that regulatory elements can exert transcriptional effects over a broad distance, in coordinating transcriptional coregulation using budding yeast, Saccharomyces cerevisiae. We empirically validated the EP model, finding that the genomic distance a promoter can affect varies by locus, which can profoundly affect levels of transcription, phenotype, and the extent of transcriptional disruption throughout a genomic region. Using the nitrogen metabolism, ribosomal protein, toxin response, and heat shock gene families as our test case, we report functionally clustered genes localize to genomic loci that are more conducive to transcriptional regulation at a distance compared to the unpaired members of the same families. Furthermore, we report that the coregulation of functional clusters is dependent, in part, on chromatin maintenance and remodeling, providing one mechanism underlying adjacent gene coregulation. IMPORTANCE The two-dimensional, physical positioning of genes along a chromosome can impact proper transcriptional regulation throughout a genomic region. The transcription of neighboring genes is correlated in a genome-wide manner, which is a characteristic of eukaryotes. Many coregulated gene families can be found clustered with another member of the same set—which can result in adjacent gene coregulation of the pair. Due to the myriad gene families that exhibit a nonrandom genomic distribution, there are likely multiple mechanisms working in concert to properly regulate transcriptional coordination of functionally clustered genes. In this study, we utilized budding yeast in an attempt to elucidate mechanisms that underlie this coregulation: testing and empirically validating the enhancer-promoter hypothesis in this species and reporting that functionally related genes cluster to genomic regions that are more conducive to transcriptional regulation at a distance. These clusters rely, in part, on chromatin maintenance and remodelers to maintain proper transcriptional coordination. Our work provides insight into the mechanisms underlying adjacent gene coregulation.Alanna CeraMaria K. HolganzaAhmad Abu HardanIrvin GamarraReem S. EldabaghMegan DeschaineSarah ElkamhawyExequiel M. SissoJonathan J. FoleyJames T. ArnoneAmerican Society for MicrobiologyarticlecoregulationgenomicsSaccharomyces cerevisiaegene expressionMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	coregulation genomics Saccharomyces cerevisiae gene expression Microbiology QR1-502
spellingShingle	coregulation genomics Saccharomyces cerevisiae gene expression Microbiology QR1-502 Alanna Cera Maria K. Holganza Ahmad Abu Hardan Irvin Gamarra Reem S. Eldabagh Megan Deschaine Sarah Elkamhawy Exequiel M. Sisso Jonathan J. Foley James T. Arnone Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
description	ABSTRACT Balancing gene expression is a fundamental challenge of all cell types. To properly regulate transcription on a genome-wide level, there are myriad mechanisms employed by the cell. One layer to this regulation is through spatial positioning, with particular chromosomal loci exerting an influence on transcription throughout a region. Many coregulated gene families utilize spatial positioning to coordinate transcription, with functionally related genes clustering together which can allow coordinated expression via adjacent gene coregulation. The mechanisms underlying this process have not been elucidated, though there are many coregulated gene families that exhibit this genomic distribution. In the present study, we tested for a role for the enhancer-promoter (EP) hypothesis, which demonstrates that regulatory elements can exert transcriptional effects over a broad distance, in coordinating transcriptional coregulation using budding yeast, Saccharomyces cerevisiae. We empirically validated the EP model, finding that the genomic distance a promoter can affect varies by locus, which can profoundly affect levels of transcription, phenotype, and the extent of transcriptional disruption throughout a genomic region. Using the nitrogen metabolism, ribosomal protein, toxin response, and heat shock gene families as our test case, we report functionally clustered genes localize to genomic loci that are more conducive to transcriptional regulation at a distance compared to the unpaired members of the same families. Furthermore, we report that the coregulation of functional clusters is dependent, in part, on chromatin maintenance and remodeling, providing one mechanism underlying adjacent gene coregulation. IMPORTANCE The two-dimensional, physical positioning of genes along a chromosome can impact proper transcriptional regulation throughout a genomic region. The transcription of neighboring genes is correlated in a genome-wide manner, which is a characteristic of eukaryotes. Many coregulated gene families can be found clustered with another member of the same set—which can result in adjacent gene coregulation of the pair. Due to the myriad gene families that exhibit a nonrandom genomic distribution, there are likely multiple mechanisms working in concert to properly regulate transcriptional coordination of functionally clustered genes. In this study, we utilized budding yeast in an attempt to elucidate mechanisms that underlie this coregulation: testing and empirically validating the enhancer-promoter hypothesis in this species and reporting that functionally related genes cluster to genomic regions that are more conducive to transcriptional regulation at a distance. These clusters rely, in part, on chromatin maintenance and remodelers to maintain proper transcriptional coordination. Our work provides insight into the mechanisms underlying adjacent gene coregulation.
format	article
author	Alanna Cera Maria K. Holganza Ahmad Abu Hardan Irvin Gamarra Reem S. Eldabagh Megan Deschaine Sarah Elkamhawy Exequiel M. Sisso Jonathan J. Foley James T. Arnone
author_facet	Alanna Cera Maria K. Holganza Ahmad Abu Hardan Irvin Gamarra Reem S. Eldabagh Megan Deschaine Sarah Elkamhawy Exequiel M. Sisso Jonathan J. Foley James T. Arnone
author_sort	Alanna Cera
title	Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_short	Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_full	Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_fullStr	Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_full_unstemmed	Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>
title_sort	functionally related genes cluster into genomic regions that coordinate transcription at a distance in <named-content content-type="genus-species">saccharomyces cerevisiae</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2536c64f8c9c40fbba13a216b00ba416
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Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in <named-content content-type="genus-species">Saccharomyces cerevisiae</named-content>

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