Nucleosome repositioning in cardiac reprogramming.
Early events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen in response to reprogramming. Histone modifi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0317718 |
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| author | Sonalí Harris Syeda S Baksh Xinghua Wang Iqra Anwar Richard E Pratt Victor J Dzau Conrad P Hodgkinson |
| author_facet | Sonalí Harris Syeda S Baksh Xinghua Wang Iqra Anwar Richard E Pratt Victor J Dzau Conrad P Hodgkinson |
| author_sort | Sonalí Harris |
| collection | DOAJ |
| description | Early events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen in response to reprogramming. Histone modification and re-positioning would be expected to open up chromatin on lineage-specific genes and this can be ascertained by studying nucleosome architecture. We have recently developed a set of tools to identify significant changes in nucleosome architecture which we used to study skeletal muscle differentiation. In this report, we have applied these tools to understand nucleosome architectural changes during fibroblast to cardiac muscle reprogramming. We found that nucleosomes surrounding the transcription start sites of cardiac muscle genes induced during reprogramming were insensitive to reprogramming factors as well as to agents which enhance reprogramming efficacy. In contrast, significant changes in nucleosome architecture were observed distal to the transcription start site. These regions were associated with nucleosome build-up. In summary, investigations into nucleosome structure do not support the notion that fibroblasts to cardiac muscle cell reprogramming involves chromatin opening and suggests instead long-range effects such as breaking closed-loop inhibition. |
| format | Article |
| id | doaj-art-1703a034b9eb405a8018dcb23ca6cd1b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1703a034b9eb405a8018dcb23ca6cd1b2025-08-20T02:12:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031771810.1371/journal.pone.0317718Nucleosome repositioning in cardiac reprogramming.Sonalí HarrisSyeda S BakshXinghua WangIqra AnwarRichard E PrattVictor J DzauConrad P HodgkinsonEarly events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen in response to reprogramming. Histone modification and re-positioning would be expected to open up chromatin on lineage-specific genes and this can be ascertained by studying nucleosome architecture. We have recently developed a set of tools to identify significant changes in nucleosome architecture which we used to study skeletal muscle differentiation. In this report, we have applied these tools to understand nucleosome architectural changes during fibroblast to cardiac muscle reprogramming. We found that nucleosomes surrounding the transcription start sites of cardiac muscle genes induced during reprogramming were insensitive to reprogramming factors as well as to agents which enhance reprogramming efficacy. In contrast, significant changes in nucleosome architecture were observed distal to the transcription start site. These regions were associated with nucleosome build-up. In summary, investigations into nucleosome structure do not support the notion that fibroblasts to cardiac muscle cell reprogramming involves chromatin opening and suggests instead long-range effects such as breaking closed-loop inhibition.https://doi.org/10.1371/journal.pone.0317718 |
| spellingShingle | Sonalí Harris Syeda S Baksh Xinghua Wang Iqra Anwar Richard E Pratt Victor J Dzau Conrad P Hodgkinson Nucleosome repositioning in cardiac reprogramming. PLoS ONE |
| title | Nucleosome repositioning in cardiac reprogramming. |
| title_full | Nucleosome repositioning in cardiac reprogramming. |
| title_fullStr | Nucleosome repositioning in cardiac reprogramming. |
| title_full_unstemmed | Nucleosome repositioning in cardiac reprogramming. |
| title_short | Nucleosome repositioning in cardiac reprogramming. |
| title_sort | nucleosome repositioning in cardiac reprogramming |
| url | https://doi.org/10.1371/journal.pone.0317718 |
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