The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong!
The expression of a large number of genes is regulated by regulatory elements that are located far away from their promoters. Identifying which gene is the target of a specific regulatory element or is affected by a non-coding mutation is often accomplished by assigning these regions to the nearest...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2022-04-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/11/4/bio059091 |
| _version_ | 1811336216222629888 |
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| author | Ellora Hui Zhen Chua Samen Yasar Nathan Harmston |
| author_facet | Ellora Hui Zhen Chua Samen Yasar Nathan Harmston |
| author_sort | Ellora Hui Zhen Chua |
| collection | DOAJ |
| description | The expression of a large number of genes is regulated by regulatory elements that are located far away from their promoters. Identifying which gene is the target of a specific regulatory element or is affected by a non-coding mutation is often accomplished by assigning these regions to the nearest gene in the genome. However, this heuristic ignores key features of genome organisation and gene regulation; in that the genome is partitioned into regulatory domains, which at some loci directly coincide with the span of topologically associated domains (TADs), and that genes are regulated by enhancers located throughout these regions, even across intervening genes. In this review, we examine the results from genome-wide studies using chromosome conformation capture technologies and from those dissecting individual gene regulatory domains, to highlight that the phenomenon of enhancer skipping is pervasive and affects multiple types of genes. We discuss how simply assigning a genomic region of interest to its nearest gene is problematic and often leads to incorrect predictions and highlight that where possible information on both the conservation and topological organisation of the genome should be used to generate better hypotheses. The article has an associated Future Leader to Watch interview. |
| first_indexed | 2024-04-13T17:36:17Z |
| format | Article |
| id | doaj.art-976d3e3088434d168bd16ad5f6c8854f |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-04-13T17:36:17Z |
| publishDate | 2022-04-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-976d3e3088434d168bd16ad5f6c8854f2022-12-22T02:37:22ZengThe Company of BiologistsBiology Open2046-63902022-04-0111410.1242/bio.059091059091The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong!Ellora Hui Zhen Chua0Samen Yasar1Nathan Harmston2 Science Division, Yale-NUS College, Singapore 138527, Singapore Science Division, Yale-NUS College, Singapore 138527, Singapore Science Division, Yale-NUS College, Singapore 138527, Singapore The expression of a large number of genes is regulated by regulatory elements that are located far away from their promoters. Identifying which gene is the target of a specific regulatory element or is affected by a non-coding mutation is often accomplished by assigning these regions to the nearest gene in the genome. However, this heuristic ignores key features of genome organisation and gene regulation; in that the genome is partitioned into regulatory domains, which at some loci directly coincide with the span of topologically associated domains (TADs), and that genes are regulated by enhancers located throughout these regions, even across intervening genes. In this review, we examine the results from genome-wide studies using chromosome conformation capture technologies and from those dissecting individual gene regulatory domains, to highlight that the phenomenon of enhancer skipping is pervasive and affects multiple types of genes. We discuss how simply assigning a genomic region of interest to its nearest gene is problematic and often leads to incorrect predictions and highlight that where possible information on both the conservation and topological organisation of the genome should be used to generate better hypotheses. The article has an associated Future Leader to Watch interview.http://bio.biologists.org/content/11/4/bio059091chromatin structureenhancersgene regulation |
| spellingShingle | Ellora Hui Zhen Chua Samen Yasar Nathan Harmston The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! Biology Open chromatin structure enhancers gene regulation |
| title | The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! |
| title_full | The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! |
| title_fullStr | The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! |
| title_full_unstemmed | The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! |
| title_short | The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong! |
| title_sort | importance of considering regulatory domains in genome wide analyses the nearest gene is often wrong |
| topic | chromatin structure enhancers gene regulation |
| url | http://bio.biologists.org/content/11/4/bio059091 |
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