Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome
ABSTRACT Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has dem...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2016-02-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-015-0240-7 |
| _version_ | 1797707930603094016 |
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| author | Zhuoya Gu Ke Jin M. James C. Crabbe Yang Zhang Xiaolin Liu Yanyan Huang Mengyi Hua Peng Nan Zhaolei Zhang Yang Zhong |
| author_facet | Zhuoya Gu Ke Jin M. James C. Crabbe Yang Zhang Xiaolin Liu Yanyan Huang Mengyi Hua Peng Nan Zhaolei Zhang Yang Zhong |
| author_sort | Zhuoya Gu |
| collection | DOAJ |
| description | ABSTRACT Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C (chromosome conformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r = 0.9, P < 2.2 × 1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation with some remote functional DNA elements like enhancers and promoters (Enhancer: hESC: r = 0.997, P = 2.3 × 10−4; IMR90: r = 0.934, P = 2 × 10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes. |
| first_indexed | 2024-03-12T06:13:46Z |
| format | Article |
| id | doaj.art-80daeb3120314d81bdffec5e4d9badde |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T06:13:46Z |
| publishDate | 2016-02-01 |
| publisher | Oxford University Press |
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| series | Protein & Cell |
| spelling | doaj.art-80daeb3120314d81bdffec5e4d9badde2023-09-03T02:47:14ZengOxford University PressProtein & Cell1674-800X1674-80182016-02-017425026610.1007/s13238-015-0240-7Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genomeZhuoya Gu0Ke Jin1M. James C. Crabbe2Yang Zhang3Xiaolin Liu4Yanyan Huang5Mengyi Hua6Peng Nan7Zhaolei Zhang8Yang Zhong9School of Life Sciences, Fudan UniversityBanting and Best Department of Medical Research, Donnelly Centre, University of TorontoDepartment of Zoology, University of OxfordDepartment of Bioengineering, University of Illinois at Urbana-ChampaignSchool of Public Health, University of MichiganSchool of Life Sciences, Fudan UniversitySchool of Life Sciences, Fudan UniversitySchool of Life Sciences, Fudan UniversityBanting and Best Department of Medical Research, Donnelly Centre, University of TorontoSchool of Life Sciences, Fudan UniversityABSTRACT Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C (chromosome conformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r = 0.9, P < 2.2 × 1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation with some remote functional DNA elements like enhancers and promoters (Enhancer: hESC: r = 0.997, P = 2.3 × 10−4; IMR90: r = 0.934, P = 2 × 10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes.http://link.springer.com/article/10.1007/s13238-015-0240-7chromatin interactionalternative parameter of Hi-C dataopen chromatinmethylation potential |
| spellingShingle | Zhuoya Gu Ke Jin M. James C. Crabbe Yang Zhang Xiaolin Liu Yanyan Huang Mengyi Hua Peng Nan Zhaolei Zhang Yang Zhong Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome Protein & Cell chromatin interaction alternative parameter of Hi-C data open chromatin methylation potential |
| title | Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome |
| title_full | Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome |
| title_fullStr | Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome |
| title_full_unstemmed | Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome |
| title_short | Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome |
| title_sort | enrichment analysis of alu elements with different spatial chromatin proximity in the human genome |
| topic | chromatin interaction alternative parameter of Hi-C data open chromatin methylation potential |
| url | http://link.springer.com/article/10.1007/s13238-015-0240-7 |
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