دورية أكاديمية
The chromatin remodeling protein Lsh alters nucleosome occupancy at putative enhancers and modulates binding of lineage specific transcription factors
| العنوان: | The chromatin remodeling protein Lsh alters nucleosome occupancy at putative enhancers and modulates binding of lineage specific transcription factors |
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| المؤلفون: | Jianke Ren, Richard Finney, Kai Ni, Maggie Cam, Kathrin Muegge |
| المصدر: | Epigenetics, Vol 14, Iss 3, Pp 277-293 (2019) |
| بيانات النشر: | Taylor & Francis Group, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | lsh, nucleosome occupancy, transcription factor, chromatin access, mnase, Genetics, QH426-470 |
| الوصف: | Dynamic regulation of chromatin accessibility is a key feature of cellular differentiation during embryogenesis, but the precise factors that control access to chromatin remain largely unknown. Lsh/HELLS is critical for normal development and mutations of Lsh in human cause the ICF (Immune deficiency, Centromeric instability, Facial anomalies) syndrome, a severe immune disorder with multiple organ deficiencies. We report here that Lsh, previously known to regulate DNA methylation level, has a genome wide chromatin remodeling function. Using micrococcal nuclease (MNase)-seq analysis, we demonstrate that Lsh protects MNase accessibility at transcriptional regulatory regions characterized by DNase I hypersensitivity and certain histone 3 (H3) tail modifications associated with enhancers. Using an auxin-inducible degron system, allowing proteolytical degradation of Lsh, we show that Lsh mediated changes in nucleosome occupancy are independent of DNA methylation level and are characterized by reduced H3 occupancy. While Lsh mediated nucleosome occupancy prevents binding sites for transcription factors in wild type cells, depletion of Lsh leads to an increase in binding of ectopically expressed tissue specific transcription factors to their respective binding sites. Our data suggests that Lsh mediated chromatin remodeling can modulate nucleosome positioning at a subset of putative enhancers contributing to the preservation of cellular identity through regulation of accessibility. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1559-2294 1559-2308 15592294 |
| Relation: | https://doaj.org/toc/1559-2294; https://doaj.org/toc/1559-2308 |
| DOI: | 10.1080/15592294.2019.1582275 |
| URL الوصول: | https://doaj.org/article/dea0b862ec064acb88bff95c4db510e6 |
| رقم الأكسشن: | edsdoj.0b862ec064acb88bff95c4db510e6 |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 15592294 15592308 |
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| DOI: | 10.1080/15592294.2019.1582275 |