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HMGB1 as a rheostat of chromatin topology and RNA homeostasis on the path to senescence [sCLIP]

ABSTRACT: HMGB1 as a rheostat of chromatin topology and RNA homeostasis on the path to senescence [sCLIP]

PROVIDER: PRJNA609118 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11194831.fastq.gz	Fastqsanger.gz
	SRR11194832.fastq.gz	Fastqsanger.gz
	SRR11194833.fastq.gz	Fastqsanger.gz
	SRR11194834.fastq.gz	Fastqsanger.gz
	SRR11194835.fastq.gz	Fastqsanger.gz

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HMGB1 as a rheostat of chromatin topology and RNA homeostasis on the path to senescence [sCLIP]

Project description: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.

2021-06-23 | GSE146047 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [ChIP-seq]

Project description:Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is perturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin and its nuclear roles. To address this, we mapped HMGB1 binding genome-wide in two primary cell lines. We integrated ChIP-seq and Hi-C with graph theory to uncover clustering of HMGB1-marked topological domains that harbour genes required for paracrine senescence. Using sCLIP and functional tests, we show that HMGB1 is also a bona fide RNA-binding protein (RBP) binding hundreds of mRNAs. It presents an interactome rich in RBPs implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and regulate the availability of SASP-relevant transcripts. Our findings highlight a broader than hitherto assumed role for HMGB1 in coordinating chromatin folding and RNA homeostasis as part of a regulatory loop controlling cell-autonomous and paracrine senescence.

2021-04-10 | GSE171781 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [Ribo-seq]

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HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [RNA-seq]

2021-04-10 | GSE171779 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence

Project description:HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence

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HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [RNA-seq]

Project description:HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [RNA-seq]

| PRJNA720946 | ENA

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [ChIP-seq]

Project description:HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [ChIP-seq]

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HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [Ribo-seq]

Project description:HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [Ribo-seq]

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HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology

Project description:DNA damage is increased in Alzheimer’s disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, in human AD postmortem brains. The abnormal phosphorylation inhibits accumulation of Ku70 to the foci of DNA double strand break (DSB), impairs DNA damage repair and eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis reveal senescence phenotypes. Extracellular high mobility group box 1 (HMGB1) protein, which is released from necrotic or hyper-activated neurons in AD, binds to toll-like receptor 4 (TLR4) of neighboring neurons, and activates protein kinase C alpha (PKCα) that executes Ku70 phosphorylation at Ser77/78. Administration of human anti-HMGB1 antibody to post-symptomatic AD model mice decreases neuronal DSBs, suppresses secondary TRIAD necrosis of neurons, prevents escalation of neurodegeneration, and ameliorates cognitive symptoms. TRIAD shares multiple features with senescence. These results newly unravel the HMGB1-Ku70 axis that accounts for the increase of neuronal DNA damage and secondary enhancement of TRIAD, the cell death phenotype of senescence, in AD.

2022-02-15 | PXD028089 | Pride

Comparison of the transcriptomes of hmgb1 vs Col-0

Project description:Testing the consequences of the absence of the chromatin-associated HMGB1 protein on the transcriptome in Arabidopsis. Keywords: Comparison of mutant and wildtype samples. Four replicate RNA extractions were performed of each genotype using independent pools of plants. hmgb1#1 (Cy5) vs. Col-0#1 (Cy3) Col-0#2 (Cy5) vs. hmgb1#2 (Cy3) dye-swap hmgb1#3 (Cy5) vs. Col-0#3 (Cy3) Col-0#5 (Cy5) vs. hmgb1#4 (Cy3) dye-swap Samples were hybridized in two dye-swaps. The data were normalized over all 4 hybridizations to obtain one, single log-ratio(Sample/Reference). The raw data files of all four of the hybridizations are attached to the Sample.

2008-11-23 | E-GEOD-10638 | biostudies-arrayexpress

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