Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters
Abstract Chromatin state is thought to impart regulatory function to the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate to one another to regulate gene expression is unclear. In this study, we have used...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Epigenetics & Chromatin |
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| Online Access: | https://doi.org/10.1186/s13072-024-00535-9 |
| _version_ | 1797233265214488576 |
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| author | Stefan A. Koestler Madeleine L. Ball Leila Muresan Vineet Dinakaran Robert White |
| author_facet | Stefan A. Koestler Madeleine L. Ball Leila Muresan Vineet Dinakaran Robert White |
| author_sort | Stefan A. Koestler |
| collection | DOAJ |
| description | Abstract Chromatin state is thought to impart regulatory function to the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate to one another to regulate gene expression is unclear. In this study, we have used super-resolution microscopy to image the Y loops of Drosophila melanogaster primary spermatocytes, which are enormous transcriptionally active chromatin fibres, each representing single transcription units that are individually resolvable in the nuclear interior. We previously found that the Y loops consist of regular clusters of nucleosomes, with an estimated median of 54 nucleosomes per cluster with wide variation. In this study, we report that the histone modifications H3K4me3, H3K27me3, and H3K36me3 are also clustered along the Y loops, with H3K4me3 more associated with diffuse chromatin compared to H3K27me3. These histone modifications form domains that can be stretches of Y loop chromatin micrometres long, or can be in short alternating domains. The different histone modifications are associated with different sizes of chromatin clusters and unique morphologies. Strikingly, a single chromatin cluster almost always only contains only one type of the histone modifications that were labelled, suggesting exclusivity, and therefore regulation at the level of individual chromatin clusters. The active mark H3K36me3 is more associated with actively elongating RNA polymerase II than H3K27me3, with polymerase often appearing on what are assumed to be looping regions on the periphery of chromatin clusters. These results provide a foundation for understanding the relationship between chromatin state, chromatin organisation, and transcription regulation – with potential implications for pause-release dynamics, splicing complex organisation and chromatin dynamics during polymerase progression along a gene. |
| first_indexed | 2024-04-24T16:13:25Z |
| format | Article |
| id | doaj.art-8bee592146c54f82971e535ec2e354ff |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-04-24T16:13:25Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-8bee592146c54f82971e535ec2e354ff2024-03-31T11:35:50ZengBMCEpigenetics & Chromatin1756-89352024-03-0117112010.1186/s13072-024-00535-9Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clustersStefan A. Koestler0Madeleine L. Ball1Leila Muresan2Vineet Dinakaran3Robert White4Department of Physiology, Development and Neuroscience, University of CambridgeDepartment of Physiology, Development and Neuroscience, University of CambridgeCambridge Advanced Imaging Centre, University of Cambridge, Downing SiteDepartment of Physiology, Development and Neuroscience, University of CambridgeDepartment of Physiology, Development and Neuroscience, University of CambridgeAbstract Chromatin state is thought to impart regulatory function to the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate to one another to regulate gene expression is unclear. In this study, we have used super-resolution microscopy to image the Y loops of Drosophila melanogaster primary spermatocytes, which are enormous transcriptionally active chromatin fibres, each representing single transcription units that are individually resolvable in the nuclear interior. We previously found that the Y loops consist of regular clusters of nucleosomes, with an estimated median of 54 nucleosomes per cluster with wide variation. In this study, we report that the histone modifications H3K4me3, H3K27me3, and H3K36me3 are also clustered along the Y loops, with H3K4me3 more associated with diffuse chromatin compared to H3K27me3. These histone modifications form domains that can be stretches of Y loop chromatin micrometres long, or can be in short alternating domains. The different histone modifications are associated with different sizes of chromatin clusters and unique morphologies. Strikingly, a single chromatin cluster almost always only contains only one type of the histone modifications that were labelled, suggesting exclusivity, and therefore regulation at the level of individual chromatin clusters. The active mark H3K36me3 is more associated with actively elongating RNA polymerase II than H3K27me3, with polymerase often appearing on what are assumed to be looping regions on the periphery of chromatin clusters. These results provide a foundation for understanding the relationship between chromatin state, chromatin organisation, and transcription regulation – with potential implications for pause-release dynamics, splicing complex organisation and chromatin dynamics during polymerase progression along a gene.https://doi.org/10.1186/s13072-024-00535-9ChromatinHistone modificationEpigenetic markTranscriptionTranscription loopNucleosome |
| spellingShingle | Stefan A. Koestler Madeleine L. Ball Leila Muresan Vineet Dinakaran Robert White Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters Epigenetics & Chromatin Chromatin Histone modification Epigenetic mark Transcription Transcription loop Nucleosome |
| title | Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| title_full | Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| title_fullStr | Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| title_full_unstemmed | Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| title_short | Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| title_sort | transcriptionally active chromatin loops contain both active and inactive histone modifications that exhibit exclusivity at the level of nucleosome clusters |
| topic | Chromatin Histone modification Epigenetic mark Transcription Transcription loop Nucleosome |
| url | https://doi.org/10.1186/s13072-024-00535-9 |
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