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Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling
During development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Alan Shepard (Shep) promotes Drosophila post-mitotic neuronal remodeling by repressing transcription...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568962/ https://www.ncbi.nlm.nih.gov/pubmed/34737269 http://dx.doi.org/10.1038/s41467-021-26628-7 |
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author | Chen, Dahong McManus, Catherine E. Radmanesh, Behram Matzat, Leah H. Lei, Elissa P. |
author_facet | Chen, Dahong McManus, Catherine E. Radmanesh, Behram Matzat, Leah H. Lei, Elissa P. |
author_sort | Chen, Dahong |
collection | PubMed |
description | During development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Alan Shepard (Shep) promotes Drosophila post-mitotic neuronal remodeling by repressing transcription of master developmental regulators, such as brain tumor (brat), specifically in maturing neurons. Since insulator proteins can promote looping, we hypothesized that Shep antagonizes brat promoter interaction with an as yet unidentified enhancer. Using chromatin conformation capture and reporter assays, we identified two enhancer regions that increase in looping frequency with the brat promoter specifically in pupal brains after Shep depletion. The brat promoters and enhancers function independently of Shep, ruling out direct repression of these elements. Moreover, ATAC-seq in isolated neurons demonstrates that Shep restricts chromatin accessibility of a key brat enhancer as well as other enhancers genome-wide in remodeling pupal but not larval neurons. These enhancers are enriched for chromatin targets of Shep and are located at Shep-inhibited genes, suggesting direct Shep inhibition of enhancer accessibility and gene expression during neuronal remodeling. Our results provide evidence for temporal regulation of chromatin looping and enhancer accessibility during neuronal maturation. |
format | Online Article Text |
id | pubmed-8568962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85689622021-11-15 Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling Chen, Dahong McManus, Catherine E. Radmanesh, Behram Matzat, Leah H. Lei, Elissa P. Nat Commun Article During development, looping of an enhancer to a promoter is frequently observed in conjunction with temporal and tissue-specific transcriptional activation. The chromatin insulator-associated protein Alan Shepard (Shep) promotes Drosophila post-mitotic neuronal remodeling by repressing transcription of master developmental regulators, such as brain tumor (brat), specifically in maturing neurons. Since insulator proteins can promote looping, we hypothesized that Shep antagonizes brat promoter interaction with an as yet unidentified enhancer. Using chromatin conformation capture and reporter assays, we identified two enhancer regions that increase in looping frequency with the brat promoter specifically in pupal brains after Shep depletion. The brat promoters and enhancers function independently of Shep, ruling out direct repression of these elements. Moreover, ATAC-seq in isolated neurons demonstrates that Shep restricts chromatin accessibility of a key brat enhancer as well as other enhancers genome-wide in remodeling pupal but not larval neurons. These enhancers are enriched for chromatin targets of Shep and are located at Shep-inhibited genes, suggesting direct Shep inhibition of enhancer accessibility and gene expression during neuronal remodeling. Our results provide evidence for temporal regulation of chromatin looping and enhancer accessibility during neuronal maturation. Nature Publishing Group UK 2021-11-04 /pmc/articles/PMC8568962/ /pubmed/34737269 http://dx.doi.org/10.1038/s41467-021-26628-7 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chen, Dahong McManus, Catherine E. Radmanesh, Behram Matzat, Leah H. Lei, Elissa P. Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title | Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title_full | Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title_fullStr | Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title_full_unstemmed | Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title_short | Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
title_sort | temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568962/ https://www.ncbi.nlm.nih.gov/pubmed/34737269 http://dx.doi.org/10.1038/s41467-021-26628-7 |
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