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Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality

BACKGROUND: Gene expression is controlled over a wide range at the transcript level through complex interplay between DNA and regulatory proteins, resulting in profiles of gene expression that can be represented as normal, graded, and bimodal (switch-like) distributions. We have previously performed...

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Autores principales: Ertel, Adam, Tozeren, Aydin
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631022/
https://www.ncbi.nlm.nih.gov/pubmed/19105848
http://dx.doi.org/10.1186/1471-2164-9-628
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author Ertel, Adam
Tozeren, Aydin
author_facet Ertel, Adam
Tozeren, Aydin
author_sort Ertel, Adam
collection PubMed
description BACKGROUND: Gene expression is controlled over a wide range at the transcript level through complex interplay between DNA and regulatory proteins, resulting in profiles of gene expression that can be represented as normal, graded, and bimodal (switch-like) distributions. We have previously performed genome-scale identification and annotation of genes with switch-like expression at the transcript level in mouse, using large microarray datasets for healthy tissue, in order to study the cellular pathways and regulatory mechanisms involving this class of genes. We showed that a large population of bimodal mouse genes encoding for cell membrane and extracellular matrix proteins is involved in communication pathways. This study expands on previous results by annotating human bimodal genes, investigating their correspondence to bimodality in mouse orthologs and exploring possible regulatory mechanisms that contribute to bimodality in gene expression in human and mouse. RESULTS: Fourteen percent of the human genes on the HGU133A array (1847 out of 13076) were identified as bimodal or switch-like. More than 40% were found to have bimodal mouse orthologs. KEGG pathways enriched for bimodal genes included ECM-receptor interaction, focal adhesion, and tight junction, showing strong similarity to the results obtained in mouse. Tissue-specific modes of expression of bimodal genes among brain, heart, and skeletal muscle were common between human and mouse. Promoter analysis revealed a higher than average number of transcription start sites per gene within the set of bimodal genes. Moreover, the bimodal gene set had differentially methylated histones compared to the set of the remaining genes in the genome. CONCLUSION: The fact that bimodal genes were enriched within the cell membrane and extracellular environment make these genes as candidates for biomarkers for tissue specificity. The commonality of the important roles bimodal genes play in tissue differentiation in both the human and mouse indicates the potential value of mouse data in providing context for human tissue studies. The regulation motifs enriched in the bimodal gene set (TATA boxes, alternative promoters, methlyation) have known associations with complex diseases, such as cancer, providing further potential for the use of bimodal genes in studying the molecular basis of disease.
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spelling pubmed-26310222009-01-27 Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality Ertel, Adam Tozeren, Aydin BMC Genomics Research Article BACKGROUND: Gene expression is controlled over a wide range at the transcript level through complex interplay between DNA and regulatory proteins, resulting in profiles of gene expression that can be represented as normal, graded, and bimodal (switch-like) distributions. We have previously performed genome-scale identification and annotation of genes with switch-like expression at the transcript level in mouse, using large microarray datasets for healthy tissue, in order to study the cellular pathways and regulatory mechanisms involving this class of genes. We showed that a large population of bimodal mouse genes encoding for cell membrane and extracellular matrix proteins is involved in communication pathways. This study expands on previous results by annotating human bimodal genes, investigating their correspondence to bimodality in mouse orthologs and exploring possible regulatory mechanisms that contribute to bimodality in gene expression in human and mouse. RESULTS: Fourteen percent of the human genes on the HGU133A array (1847 out of 13076) were identified as bimodal or switch-like. More than 40% were found to have bimodal mouse orthologs. KEGG pathways enriched for bimodal genes included ECM-receptor interaction, focal adhesion, and tight junction, showing strong similarity to the results obtained in mouse. Tissue-specific modes of expression of bimodal genes among brain, heart, and skeletal muscle were common between human and mouse. Promoter analysis revealed a higher than average number of transcription start sites per gene within the set of bimodal genes. Moreover, the bimodal gene set had differentially methylated histones compared to the set of the remaining genes in the genome. CONCLUSION: The fact that bimodal genes were enriched within the cell membrane and extracellular environment make these genes as candidates for biomarkers for tissue specificity. The commonality of the important roles bimodal genes play in tissue differentiation in both the human and mouse indicates the potential value of mouse data in providing context for human tissue studies. The regulation motifs enriched in the bimodal gene set (TATA boxes, alternative promoters, methlyation) have known associations with complex diseases, such as cancer, providing further potential for the use of bimodal genes in studying the molecular basis of disease. BioMed Central 2008-12-23 /pmc/articles/PMC2631022/ /pubmed/19105848 http://dx.doi.org/10.1186/1471-2164-9-628 Text en Copyright © 2008 Ertel and Tozeren; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ertel, Adam
Tozeren, Aydin
Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title_full Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title_fullStr Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title_full_unstemmed Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title_short Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
title_sort human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631022/
https://www.ncbi.nlm.nih.gov/pubmed/19105848
http://dx.doi.org/10.1186/1471-2164-9-628
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