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Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae

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...

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Autores principales: Cera, Alanna, Holganza, Maria K., Hardan, Ahmad Abu, Gamarra, Irvin, Eldabagh, Reem S., Deschaine, Megan, Elkamhawy, Sarah, Sisso, Exequiel M., Foley, Jonathan J., Arnone, James T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416364/
https://www.ncbi.nlm.nih.gov/pubmed/30867326
http://dx.doi.org/10.1128/mSphere.00063-19
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author Cera, Alanna
Holganza, Maria K.
Hardan, Ahmad Abu
Gamarra, Irvin
Eldabagh, Reem S.
Deschaine, Megan
Elkamhawy, Sarah
Sisso, Exequiel M.
Foley, Jonathan J.
Arnone, James T.
author_facet Cera, Alanna
Holganza, Maria K.
Hardan, Ahmad Abu
Gamarra, Irvin
Eldabagh, Reem S.
Deschaine, Megan
Elkamhawy, Sarah
Sisso, Exequiel M.
Foley, Jonathan J.
Arnone, James T.
author_sort Cera, Alanna
collection PubMed
description 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.
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spelling pubmed-64163642019-04-03 Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae Cera, Alanna Holganza, Maria K. Hardan, Ahmad Abu Gamarra, Irvin Eldabagh, Reem S. Deschaine, Megan Elkamhawy, Sarah Sisso, Exequiel M. Foley, Jonathan J. Arnone, James T. mSphere Research Article 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. American Society for Microbiology 2019-03-13 /pmc/articles/PMC6416364/ /pubmed/30867326 http://dx.doi.org/10.1128/mSphere.00063-19 Text en Copyright © 2019 Cera et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Cera, Alanna
Holganza, Maria K.
Hardan, Ahmad Abu
Gamarra, Irvin
Eldabagh, Reem S.
Deschaine, Megan
Elkamhawy, Sarah
Sisso, Exequiel M.
Foley, Jonathan J.
Arnone, James T.
Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title_full Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title_fullStr Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title_full_unstemmed Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title_short Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
title_sort functionally related genes cluster into genomic regions that coordinate transcription at a distance in saccharomyces cerevisiae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416364/
https://www.ncbi.nlm.nih.gov/pubmed/30867326
http://dx.doi.org/10.1128/mSphere.00063-19
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