Dynamic enhancer interactome promotes senescence and aging [Hi-ChIP II]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1066357 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27638367_1.fastq.gz | Fastqsanger.gz | |||
| SRR27638367_2.fastq.gz | Fastqsanger.gz | |||
| SRR27638368_1.fastq.gz | Fastqsanger.gz | |||
| SRR27638368_2.fastq.gz | Fastqsanger.gz | |||
| SRR27638369_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Dynamic enhancer interactome promotes senescence and aging [Hi-ChIP I]
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Project description:Dynamic enhancer interactome promotes senescence and aging
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Project description:Gene expression programs are regulated by enhancers which act in a context-specific manner, and can reside at great distances from their target genes. Extensive three-dimensional (3D) genome reorganization occurs in senescence, but how enhancer interactomes are reconfigured during this process is just beginning to be understood. Here we generated high-resolution contact maps of active enhancers and their target genes, assessed chromatin accessibility, and established one-dimensional maps of various histone modifications and transcription factors to comprehensively understand the regulation of enhancer configuration during senescence. Hyper-connected enhancer communities/cliques formed around genes that are highly expressed and within essential gene pathways in each cell state. In addition, motif analysis indicates the involvement of specific transcription factors in hyper-connected regulatory elements in each condition; importantly, MafK, a bZIP family transcription factor, was upregulated in senescence, and reduced expression of MafK ameliorated the senescence phenotypes. Because the accumulation of senescent cells is a key feature of aging, we further investigated enhancer connectomes in the liver of young and aged mice. Hyper-connected enhancer communities were identified during aging, which regulate essential genes that maintain cell differentiation and homeostasis. These findings reveal that hyper-connected enhancer communities correlate with high gene expression in senescence and aging and provide potential hotspots for therapeutic intervention in aging and age-associated diseases.
2023-06-20 | GSE232942 | GEO
Project description:Gene expression programs are regulated by enhancers which act in a context-specific manner, and can reside at great distances from their target genes. Extensive three-dimensional (3D) genome reorganization occurs in senescence, but how enhancer interactomes are reconfigured during this process is just beginning to be understood. Here we generated high-resolution contact maps of active enhancers and their target genes, assessed chromatin accessibility, and established one-dimensional maps of various histone modifications and transcription factors to comprehensively understand the regulation of enhancer configuration during senescence. Hyper-connected enhancer communities/cliques formed around genes that are highly expressed and within essential gene pathways in each cell state. In addition, motif analysis indicates the involvement of specific transcription factors in hyper-connected regulatory elements in each condition; importantly, MafK, a bZIP family transcription factor, was upregulated in senescence, and reduced expression of MafK ameliorated the senescence phenotypes. Because the accumulation of senescent cells is a key feature of aging, we further investigated enhancer connectomes in the liver of young and aged mice. Hyper-connected enhancer communities were identified during aging, which regulate essential genes that maintain cell differentiation and homeostasis. These findings reveal that hyper-connected enhancer communities correlate with high gene expression in senescence and aging and provide potential hotspots for therapeutic intervention in aging and age-associated diseases.
2024-10-31 | GSE253617 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-18 | GSE253618 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging. In this study, we show that histone lactylation plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation and lactyl-CoA levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Modulating the enzymes also leads to the loss of histone lactylation in skeletal muscle, downregulating DNA repair and proteostasis pathways and accelerating muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence and muscle aging, suggesting that this modification may serve as an innovative biomarker for senescence.
2024-05-01 | GSE226005 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging. In this study, we show that histone lactylation plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation and lactyl-CoA levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Modulating the enzymes also leads to the loss of histone lactylation in skeletal muscle, downregulating DNA repair and proteostasis pathways and accelerating muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence and muscle aging, suggesting that this modification may serve as an innovative biomarker for senescence.
2024-05-01 | GSE226007 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging. In this study, we show that histone lactylation plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation and lactyl-CoA levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Modulating the enzymes also leads to the loss of histone lactylation in skeletal muscle, downregulating DNA repair and proteostasis pathways and accelerating muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence and muscle aging, suggesting that this modification may serve as an innovative biomarker for senescence.
2024-05-01 | GSE226006 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging. In this study, we show that histone lactylation plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation and lactyl-CoA levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Modulating the enzymes also leads to the loss of histone lactylation in skeletal muscle, downregulating DNA repair and proteostasis pathways and accelerating muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence and muscle aging, suggesting that this modification may serve as an innovative biomarker for senescence.
2024-05-01 | GSE249561 | GEO
Project description:Cellular senescence is an irreversible cell growth arrest state linked to loss of tissue function and aging in mammals. The cellular transition from proliferation to senescence is marked by increased expression of the cell-cycle inhibitor p16INK4A and formation of senescence-associated heterochromatin foci (SAHF). It is known that SAHF formation depends primarily on HIRA-mediated nucleosome assembly of H3.3, and that the serine/threonine protein kinase Pak2 regulates HIRA-mediated nucleosome assembly of histone H3.3. Here, we tested the role of Pak2 in the regulation of cellular senescence. Depletion of Pak2 delays premature cellular senescence in both oncogene-induced senescence in human fibroblasts IMR90 cells and in oxidative stress induced senescence of mouse embryonic fibroblasts. Furthermore, overexpression of Pak2 promotes senescence of IMR90 cells. Importantly, depletion of Pak2 in mice delays the onset of some of the aging-associated phenotypes and extend life span of a progeroid mouse model. Lastly, we showed that Pak2 is required for expression of a group of genes involved in cellular senescence and regulates the deposition of newly synthesized H3.3 onto chromatin in senescent cells. Together, our results demonstrate that Pak2 is an important regulator of cellular senescence and organismal aging, in part through the regulation of gene expression and H3.3 nucleosome assembly.
2019-12-31 | GSE108081 | GEO