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Understanding Tissue-Specific Gene Regulation

Although all human tissues carry out common processes, tissues are distinguished by gene expression patterns, implying that distinct regulatory programs control tissue specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expressi...

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Autores principales: Sonawane, Abhijeet Rajendra, Platig, John, Fagny, Maud, Chen, Cho-Yi, Paulson, Joseph Nathaniel, Lopes-Ramos, Camila Miranda, DeMeo, Dawn Lisa, Quackenbush, John, Glass, Kimberly, Kuijjer, Marieke Lydia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828531/
https://www.ncbi.nlm.nih.gov/pubmed/29069589
http://dx.doi.org/10.1016/j.celrep.2017.10.001
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author Sonawane, Abhijeet Rajendra
Platig, John
Fagny, Maud
Chen, Cho-Yi
Paulson, Joseph Nathaniel
Lopes-Ramos, Camila Miranda
DeMeo, Dawn Lisa
Quackenbush, John
Glass, Kimberly
Kuijjer, Marieke Lydia
author_facet Sonawane, Abhijeet Rajendra
Platig, John
Fagny, Maud
Chen, Cho-Yi
Paulson, Joseph Nathaniel
Lopes-Ramos, Camila Miranda
DeMeo, Dawn Lisa
Quackenbush, John
Glass, Kimberly
Kuijjer, Marieke Lydia
author_sort Sonawane, Abhijeet Rajendra
collection PubMed
description Although all human tissues carry out common processes, tissues are distinguished by gene expression patterns, implying that distinct regulatory programs control tissue specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that the regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes.
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spelling pubmed-58285312018-10-24 Understanding Tissue-Specific Gene Regulation Sonawane, Abhijeet Rajendra Platig, John Fagny, Maud Chen, Cho-Yi Paulson, Joseph Nathaniel Lopes-Ramos, Camila Miranda DeMeo, Dawn Lisa Quackenbush, John Glass, Kimberly Kuijjer, Marieke Lydia Cell Rep Article Although all human tissues carry out common processes, tissues are distinguished by gene expression patterns, implying that distinct regulatory programs control tissue specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that the regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes. 2017-10-24 /pmc/articles/PMC5828531/ /pubmed/29069589 http://dx.doi.org/10.1016/j.celrep.2017.10.001 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license.
spellingShingle Article
Sonawane, Abhijeet Rajendra
Platig, John
Fagny, Maud
Chen, Cho-Yi
Paulson, Joseph Nathaniel
Lopes-Ramos, Camila Miranda
DeMeo, Dawn Lisa
Quackenbush, John
Glass, Kimberly
Kuijjer, Marieke Lydia
Understanding Tissue-Specific Gene Regulation
title Understanding Tissue-Specific Gene Regulation
title_full Understanding Tissue-Specific Gene Regulation
title_fullStr Understanding Tissue-Specific Gene Regulation
title_full_unstemmed Understanding Tissue-Specific Gene Regulation
title_short Understanding Tissue-Specific Gene Regulation
title_sort understanding tissue-specific gene regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828531/
https://www.ncbi.nlm.nih.gov/pubmed/29069589
http://dx.doi.org/10.1016/j.celrep.2017.10.001
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