Similar Datasets
Project description:Dramatic alterations in epigenetic landscapes are known to affect genome accessibility and their transcriptional program. Extensive evidences have emerged that senescent cells accumulate profound chromatin tremendous reordering upon senescence entry, yet, the underlying mechanisms between epigenetic parameters and gene expression profile have not been fully clarified. In this report, we delineate the genome-wide redistribution of accessible chromatin regions leading to broad transcriptome effects during UC-MSCs senescence. We report the distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac decorated enhancer regions, where the SAAs are responsible for elevated flanking SASP expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, shifting away from H3K27ac-labled SAAs and leading to prominent chromatin accessibility reconstruction during senescence. The enhanced signal of SAAs driven by TEAD4 suppression subsequently induce a robust decrease of adjacent SASP genes expression and downstream factors secretion, and finally, contributing to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry and reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulate the overall transcriptional program of the SASP genes.
2023-04-01 | GSE226287 | GEO
Project description:Dramatic alterations in epigenetic landscapes are known to affect genome accessibility and their transcriptional program. Extensive evidences have emerged that senescent cells accumulate profound chromatin tremendous reordering upon senescence entry, yet, the underlying mechanisms between epigenetic parameters and gene expression profile have not been fully clarified. In this report, we delineate the genome-wide redistribution of accessible chromatin regions leading to broad transcriptome effects during UC-MSCs senescence. We report the distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac decorated enhancer regions, where the SAAs are responsible for elevated flanking SASP expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, shifting away from H3K27ac-labled SAAs and leading to prominent chromatin accessibility reconstruction during senescence. The enhanced signal of SAAs driven by TEAD4 suppression subsequently induce a robust decrease of adjacent SASP genes expression and downstream factors secretion, and finally, contributing to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry and reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulate the overall transcriptional program of the SASP genes.
2023-04-01 | GSE226325 | GEO
Project description:Dramatic alterations in epigenetic landscapes are known to affect genome accessibility and their transcriptional program. Extensive evidences have emerged that senescent cells accumulate profound chromatin tremendous reordering upon senescence entry, yet, the underlying mechanisms between epigenetic parameters and gene expression profile have not been fully clarified. In this report, we delineate the genome-wide redistribution of accessible chromatin regions leading to broad transcriptome effects during UC-MSCs senescence. We report the distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac decorated enhancer regions, where the SAAs are responsible for elevated flanking SASP expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, shifting away from H3K27ac-labled SAAs and leading to prominent chromatin accessibility reconstruction during senescence. The enhanced signal of SAAs driven by TEAD4 suppression subsequently induce a robust decrease of adjacent SASP genes expression and downstream factors secretion, and finally, contributing to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry and reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulate the overall transcriptional program of the SASP genes.
2023-04-01 | GSE226294 | GEO
Project description:Dramatic alterations in epigenetic landscapes are known to impact genome accessibility and transcription. Extensive evidence demonstrates that senescent cells undergo significant changes in chromatin structure; however, the mechanisms underlying the crosstalk between epigenetic parameters and gene expression profiles have not been fully elucidated. In the present study, we delineate the genome-wide redistribution of accessible chromatin regions that lead to broad transcriptome effects during senescence. We report that distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac-occupied enhancer regions, where they are responsible for elevated flanking senescence-associated secretory phenotype (SASP) expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, moves away from H3K27ac-labled SAAs to allow for prominent chromatin accessibility reconstruction during senescence. The enhanced SAAs signal driven by TEAD4 suppression subsequently induces a robust increase in the expression of adjacent SASP genes and the secretion of downstream factors, which contribute to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry, and further reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulates the overall transcriptional program of SASP genes.
| S-EPMC10587282 | biostudies-literature
Project description:TEAD4 delays cellular senescence by remodeling chromatin accessibility at H3K27ac-occupied enhancer regions
| PRJNA939704 | ENA
Project description:TEAD4 delays cellular senescence by remodeling chromatin accessibility at H3K27ac-occupied enhancer regions [ATAC-seq]
| PRJNA939545 | ENA
Project description:TEAD4 delays cellular senescence by remodeling chromatin accessibility at H3K27ac-occupied enhancer regions [CUT&Tag]
| PRJNA939566 | ENA
Project description:TEAD4 delays cellular senescence by remodeling chromatin accessibility at H3K27ac-occupied enhancer regions [RNA-seq]
| PRJNA939707 | ENA
Project description:Enhancers are cis-acting elements capable of regulating transcription in a distance and orientation-independent manner. A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. We thoroughly investigated the association between eRNA productivity and various chromatin marks and transcriptional regulators in mouse embryonic stem cells (ESCs) through an integrative approach. We found that eRNA-producing enhancers exhibited elevated levels of the active mark H3K27Ac, decreased DNA methylation, and enrichment for the DNA hydroxylase Tet1. Many eRNA-producing enhancers have recently been characterized as "super-enhancers," suggesting an important role in the maintenance of pluripotency. Using experimental methods, we focally investigated a well-characterized enhancer linked to the Nanog locus and confirmed its exclusive eRNA productivity in ESCs. We further demonstrate that the binding of Sall4 and Tet family proteins were required for eRNA productivity at this locus. Collectively, we demonstrate that Tet1 binding and DNA hypomethylation are hallmarks of eRNA production.
| S-EPMC3933491 | biostudies-literature
Project description:Notch signaling plays a key role in many cell fate decisions during development by directing different gene expression programs via the transcription factor CSL, known as Su(H) in Drosophila Which target genes are responsive to Notch signaling is influenced by the chromatin state of enhancers, yet how this is regulated is not fully known. Detecting a specific increase in the histone variant H3.3 in response to Notch signaling, we tested which chromatin remodelers or histone chaperones are required for the changes in enhancer accessibility to Su(H) binding. We show a crucial role for the Brahma SWI/SNF chromatin remodeling complex, including the actin-related BAP55 subunit, in conferring enhancer accessibility and enabling the transcriptional response to Notch activity. The Notch-responsive regions have high levels of nucleosome turnover which depend on the Brahma complex, increase in magnitude with Notch signaling, and primarily involve histone H3.3. Together these results highlight the importance of SWI/SNF-mediated nucleosome turnover in rendering enhancers responsive to Notch.
| S-EPMC6500979 | biostudies-literature