Similar Datasets
Project description:Reactive oxygen species (ROS) are important signalling molecules in many physiological processes, yet excess ROS leads to cell damage and can lead to pathology. Accordingly, cells need to maintain tight regulation of ROS levels, and ROS-responsive transcriptional reprogramming is central to this process. Although it has long been recognized that oxidative stress leads to rapid, significant changes in gene expression, the impact of oxidative stress on the underlying chromatin accessibility landscape remained unclear. Here, we asked whether ROS-responsive transcriptional reprogramming is accompanied by reprogramming of the chromatin environment in MCF7 human breast cancer cells. Using a time-course exposure to multiple inducers of oxidative stress, we determined that the widespread ROS-responsive changes in gene expression induced by ROS occur with minimal changes to the chromatin environment. While we did observe changes in chromatin accessibility, these changes were: (1) far less numerous than gene expression changes after oxidative stress, and (2) occur within pre-existing regions of accessible chromatin. TF footprinting analysis identified 5 TFs or TF families with evidence for ROS-responsive changes in DNA binding: NRF2, AP-1, p53, NFY, and SP/KLF. Importantly, several of these (AP-1, NF- Y, and SP/KLF factors) have not been previously implicated as widespread regulators in the response to ROS. In summary, we have characterized genome-wide changes in gene expression and chromatin accessibility in response to ROS treatment of MCF7 cells, and we have found that regulation of the large-scale transcriptional response to excess ROS is primarily constrained by the cell’s pre-existing chromatin landscape.
2021-05-07 | GSE173663 | GEO
Project description:Reactive oxygen species (ROS) are important signalling molecules in many physiological processes, yet excess ROS leads to cell damage and can lead to pathology. Accordingly, cells need to maintain tight regulation of ROS levels, and ROS-responsive transcriptional reprogramming is central to this process. Although it has long been recognized that oxidative stress leads to rapid, significant changes in gene expression, the impact of oxidative stress on the underlying chromatin accessibility landscape remained unclear. Here, we asked whether ROS-responsive transcriptional reprogramming is accompanied by reprogramming of the chromatin environment in MCF7 human breast cancer cells. Using a time-course exposure to multiple inducers of oxidative stress, we determined that the widespread ROS-responsive changes in gene expression induced by ROS occur with minimal changes to the chromatin environment. While we did observe changes in chromatin accessibility, these changes were: (1) far less numerous than gene expression changes after oxidative stress, and (2) occur within pre-existing regions of accessible chromatin. TF footprinting analysis identified 5 TFs or TF families with evidence for ROS-responsive changes in DNA binding: NRF2, AP-1, p53, NFY, and SP/KLF. Importantly, several of these (AP-1, NF- Y, and SP/KLF factors) have not been previously implicated as widespread regulators in the response to ROS. In summary, we have characterized genome-wide changes in gene expression and chromatin accessibility in response to ROS treatment of MCF7 cells, and we have found that regulation of the large-scale transcriptional response to excess ROS is primarily constrained by the cell’s pre-existing chromatin landscape.
2021-05-07 | GSE173662 | GEO
Project description:Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape
| PRJNA726553 | ENA
Project description:Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape [ATAC-seq]
| PRJNA726557 | ENA
Project description:Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape [RNA-seq]
| PRJNA726556 | ENA
Project description:Oocytes have a remarkable ability to reactivate silenced genes in somatic cells. However, it is not clear how the chromatin architecture of somatic cells affects this transcriptional reprogramming. Here, we investigated the relationship between the chromatin opening and transcriptional activation. We reveal changes in chromatin accessibility and their relevance to transcriptional reprogramming after transplantation of somatic nuclei into Xenopus oocytes. Genes that are silenced, but have pre-existing open transcription start sites in donor cells, are prone to be activated after nuclear transfer, suggesting that the chromatin signature of somatic nuclei influences transcriptional reprogramming. There are also activated genes associated with new open chromatin sites, and transcription factors in oocytes play an important role in transcriptional reprogramming from such genes. Finally, we show that genes resistant to reprogramming are associated with closed chromatin configurations. We conclude that chromatin accessibility is a central factor for successful transcriptional reprogramming in oocytes.
| S-EPMC6057489 | biostudies-literature
Project description:Medaka (Oryzias latipes) has become an important vertebrate model widely used in genetics, developmental biology, environmental sciences, and many other fields. A high-quality genome sequence and a variety of genetic tools are available for this model organism. However, existing genome annotation is still rudimentary, as it was mainly based on computational prediction and short-read RNA-seq data. Here we report a dynamic transcriptome landscape of medaka embryogenesis profiled by long-read RNA-seq, short-read RNA-seq, and ATAC-seq. By integrating these data sets, we constructed a much-improved gene model set including about 17,000 novel isoforms and identified 1600 transcription factors, 1100 long noncoding RNAs, and 150,000 potential cis-regulatory elements as well. Time-series data sets provided another dimension of information. With the expression dynamics of genes and accessibility dynamics of cis-regulatory elements, we investigated isoform switching, as well as regulatory logic between accessible elements and genes, during embryogenesis. We built a user-friendly medaka omics data portal to present these data sets. This resource provides the first comprehensive omics data sets of medaka embryogenesis. Ultimately, we term these three assays as the minimum ENCODE toolbox and propose the use of it as the initial and essential profiling genomic assays for model organisms that have limited data available. This work will be of great value for the research community using medaka as the model organism and many others as well.
| S-EPMC7370878 | biostudies-literature
Project description:Gata4, Hand2, Mef2c, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here, we explore the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and the endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.
| S-EPMC6657359 | biostudies-literature
Project description:Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to "remember" their initial environmental encounter.
| S-EPMC5357947 | biostudies-literature
Project description: Not available
| S-EPMC8181391 | biostudies-literature