Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain
Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our sp...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471400802X |
| _version_ | 1811213449306308608 |
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| author | Marit W. Vermunt Peter Reinink Jeroen Korving Ewart de Bruijn Paul M. Creyghton Onur Basak Geert Geeven Pim W. Toonen Nico Lansu Charles Meunier Sebastiaan van Heesch Hans Clevers Wouter de Laat Edwin Cuppen Menno P. Creyghton |
| author_facet | Marit W. Vermunt Peter Reinink Jeroen Korving Ewart de Bruijn Paul M. Creyghton Onur Basak Geert Geeven Pim W. Toonen Nico Lansu Charles Meunier Sebastiaan van Heesch Hans Clevers Wouter de Laat Edwin Cuppen Menno P. Creyghton |
| author_sort | Marit W. Vermunt |
| collection | DOAJ |
| description | Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson’s disease incidence. |
| first_indexed | 2024-04-12T05:46:55Z |
| format | Article |
| id | doaj.art-f2a52140da1e424a8aff2a3ac40ccfd4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T05:46:55Z |
| publishDate | 2014-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f2a52140da1e424a8aff2a3ac40ccfd42022-12-22T03:45:26ZengElsevierCell Reports2211-12472014-10-019276777910.1016/j.celrep.2014.09.023Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human BrainMarit W. Vermunt0Peter Reinink1Jeroen Korving2Ewart de Bruijn3Paul M. Creyghton4Onur Basak5Geert Geeven6Pim W. Toonen7Nico Lansu8Charles Meunier9Sebastiaan van Heesch10Hans Clevers11Wouter de Laat12Edwin Cuppen13Menno P. Creyghton14Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsHubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, the NetherlandsUnderstanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson’s disease incidence.http://www.sciencedirect.com/science/article/pii/S221112471400802X |
| spellingShingle | Marit W. Vermunt Peter Reinink Jeroen Korving Ewart de Bruijn Paul M. Creyghton Onur Basak Geert Geeven Pim W. Toonen Nico Lansu Charles Meunier Sebastiaan van Heesch Hans Clevers Wouter de Laat Edwin Cuppen Menno P. Creyghton Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain Cell Reports |
| title | Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain |
| title_full | Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain |
| title_fullStr | Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain |
| title_full_unstemmed | Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain |
| title_short | Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain |
| title_sort | large scale identification of coregulated enhancer networks in the adult human brain |
| url | http://www.sciencedirect.com/science/article/pii/S221112471400802X |
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