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| Status |
Public on Jun 23, 2021 |
| Title |
HMGB1 as a rheostat of chromatin topology and RNA homeostasis on the path to senescence [sCLIP] |
| Organism |
Homo sapiens |
| Experiment type |
Other
Expression profiling by high throughput sequencing
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| Summary |
Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This link is perturbed once cells enter senescence. The highly abundant HMGB1 protein, known to associate with bent and looped DNA, is actively depleted from senescent cell nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we still lack understanding of the positioning and functional roles of HMGB1 on chromatin in vivo. To address this, we mapped HMGB1 binding genome-wide in different primary cells using a tailored protocol. We then integrated ChIP-seq and Hi-C data with a knot theory approach to uncover HMGB1 demarcation at the boundaries of particular topologically-associating domains (TADs). These TADs harbor genes involved in the key proinflammatory leg of the senescent transcriptional program. Moreover, we used sCLIP and siRNA-mediated knockdown to show that HMGB1 is a bona fide RNA-binding protein also affecting splicing choices. Together, our findings highlight a broader than hitherto assumed role for HMGB1 in chromatin homeostasis connected to cell cycle potency, and allow us to postulate a rheostat model for HMGB function with implications in cancer biology.
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| Overall design |
sCLIP was performed to assess the RNA-binding properties of HMGB1 and HMGB2 proteins in human fibroblast cell line IMR90-79 .
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| Contributor(s) |
Kargapolova Y, Papantonis A |
| Citation(s) |
34166567 |
| Submission date |
Feb 27, 2020 |
| Last update date |
Sep 22, 2021 |
| Contact name |
Yulia Kargapolova |
| Organization name |
Cologne University
|
| Department |
CMMC
|
| Lab |
AG Papantonis
|
| Street address |
Robert-Koch-Straße 21
|
| City |
Cologne |
| ZIP/Postal code |
50931 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE171782 |
HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence |
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| Relations |
| BioProject |
PRJNA609118 |
| SRA |
SRP250967 |
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