Integration of RNA-Seq and ATAC-Seq Identifies Key Genes and chromatin accessibility changes in Growth hormone-secreting pituitary adenoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE182180 | GEO | 2021/08/18
REPOSITORIES: GEO
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Project description:Suspended animation (e.g. hibernation, diapause) allows organisms to survive extreme environments. But the mechanisms underlying the evolution of suspended animation states are unknown. The African turquoise killifish has evolved diapause as a form of suspended development to survive the complete drought that occurs every summer. Here, we show that gene duplicates – paralogs – exhibit specialized expression in diapause compared to normal development in the African turquoise killifish. Surprisingly, paralogs with specialized expression in diapause are evolutionarily very ancient and are present even in vertebrates that do not exhibit diapause. To determine if evolution of diapause is due to the regulatory landscape rewiring at ancient paralogs, we assessed chromatin accessibility genome-wide in fish species with or without diapause. This analysis revealed an evolutionary recent increase in chromatin accessibility at very ancient paralogs in African turquoise killifish. The increase in chromatin accessibility is linked to the presence of new binding sites for transcription factors, likely due to de novo mutations and transposable element (TE) insertion. Interestingly, accessible chromatin regions in diapause are enriched for lipid metabolism genes, and our lipidomics studies uncover a striking difference in lipid species in African turquoise killifish diapause, which could be critical for long-term survival. Together, our results show that diapause likely originated by repurposing pre-existing gene programs via recent changes in the regulatory landscape. This work raises the possibility that suspended animation programs could be reactivated in other species for long-term preservation via transcription factor remodeling and suggests a mechanism for how complex adaptations evolve in nature.
2021-08-05 | ST001898 | MetabolomicsWorkbench
Project description:Hormone dependent uterine gene expression changes that occur during the estrous cycle suggest hormone receptor binding to chromatin may also be dynamic. Therefore, we employed a multi-faceted approach to examine in vivo dynamics of hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq for estrogen receptor alpha (ERα) and progesterone receptor (PGR). Genome wide, there were extensive estrous cycle dependent changes in ERα and PGR binding as well as chromatin accessibility. There were 4,159 differentially expressed genes between estrus and diestrus. At transcription start sites, accessibility generally correlated with the directionality of gene expression and there was reduced PGR in estrus compared to diestrus but little change in ERα. There were 2,727 enhancers with dynamic accessibility near these genes and 77% of those correlated with directionality of gene expression changes. However, most enhancers were constitutively open (8,694). In both dynamic and constitutively open enhancers, ERα and PgR binding was coordinately lost from diestrus to estrus. Diestrus specific ERα binding and accessible regions were enriched for PGR, FOX, GATA and SOX binding motifs. In contrast, estrus specific ERα binding occurred at transcription factor deserts in relatively closed chromatin while estrus specific accessible regions were highly enriched for ATF, ELF and ELK motifs. Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (RIME) revealed many estrous cycle dependent partners of ERα (diestrus, 60; estrus, 24). PGR was found in complex with ERα during diestrus but not estrus supporting coordinated binding of both receptors during diestrus. Two of the cohesin complex proteins, SMC1A and SMC3, were found in complex with ERα during diestrus but not estrus; overlap of SMC1A with ERα confirmed this preferential interaction during diestrus. Additionally, HiC analysis showed more diestrus specific interactions than estrus (476 versus 263) suggesting the SMC1A/ ERα interactions have functional consequences on chromatin structure. Taken together, a complex series of interactions between hormone receptors, chromatin structure and accessibility orchestrate estrous cycle dependent changes in gene expression.
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Project description:Hormone dependent uterine gene expression changes that occur during the estrous cycle suggest hormone receptor binding to chromatin may also be dynamic. Therefore, we employed a multi-faceted approach to examine in vivo dynamics of hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq for estrogen receptor alpha (ERα) and progesterone receptor (PGR). Genome wide, there were extensive estrous cycle dependent changes in ERα and PGR binding as well as chromatin accessibility. There were 4,159 differentially expressed genes between estrus and diestrus. At transcription start sites, accessibility generally correlated with the directionality of gene expression and there was reduced PGR in estrus compared to diestrus but little change in ERα. There were 2,727 enhancers with dynamic accessibility near these genes and 77% of those correlated with directionality of gene expression changes. However, most enhancers were constitutively open (8,694). In both dynamic and constitutively open enhancers, ERα and PgR binding was coordinately lost from diestrus to estrus. Diestrus specific ERα binding and accessible regions were enriched for PGR, FOX, GATA and SOX binding motifs. In contrast, estrus specific ERα binding occurred at transcription factor deserts in relatively closed chromatin while estrus specific accessible regions were highly enriched for ATF, ELF and ELK motifs. Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (RIME) revealed many estrous cycle dependent partners of ERα (diestrus, 60; estrus, 24). PGR was found in complex with ERα during diestrus but not estrus supporting coordinated binding of both receptors during diestrus. Two of the cohesin complex proteins, SMC1A and SMC3, were found in complex with ERα during diestrus but not estrus; overlap of SMC1A with ERα confirmed this preferential interaction during diestrus. Additionally, HiC analysis showed more diestrus specific interactions than estrus (476 versus 263) suggesting the SMC1A/ ERα interactions have functional consequences on chromatin structure. Taken together, a complex series of interactions between hormone receptors, chromatin structure and accessibility orchestrate estrous cycle dependent changes in gene expression.
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Project description:Hormone dependent uterine gene expression changes that occur during the estrous cycle suggest hormone receptor binding to chromatin may also be dynamic. Therefore, we employed a multi-faceted approach to examine in vivo dynamics of hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq for estrogen receptor alpha (ERα) and progesterone receptor (PGR). Genome wide, there were extensive estrous cycle dependent changes in ERα and PGR binding as well as chromatin accessibility. There were 4,159 differentially expressed genes between estrus and diestrus. At transcription start sites, accessibility generally correlated with the directionality of gene expression and there was reduced PGR in estrus compared to diestrus but little change in ERα. There were 2,727 enhancers with dynamic accessibility near these genes and 77% of those correlated with directionality of gene expression changes. However, most enhancers were constitutively open (8,694). In both dynamic and constitutively open enhancers, ERα and PgR binding was coordinately lost from diestrus to estrus. Diestrus specific ERα binding and accessible regions were enriched for PGR, FOX, GATA and SOX binding motifs. In contrast, estrus specific ERα binding occurred at transcription factor deserts in relatively closed chromatin while estrus specific accessible regions were highly enriched for ATF, ELF and ELK motifs. Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (RIME) revealed many estrous cycle dependent partners of ERα (diestrus, 60; estrus, 24). PGR was found in complex with ERα during diestrus but not estrus supporting coordinated binding of both receptors during diestrus. Two of the cohesin complex proteins, SMC1A and SMC3, were found in complex with ERα during diestrus but not estrus; overlap of SMC1A with ERα confirmed this preferential interaction during diestrus. Additionally, HiC analysis showed more diestrus specific interactions than estrus (476 versus 263) suggesting the SMC1A/ ERα interactions have functional consequences on chromatin structure. Taken together, a complex series of interactions between hormone receptors, chromatin structure and accessibility orchestrate estrous cycle dependent changes in gene expression.
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Project description:Hormone dependent uterine gene expression changes that occur during the estrous cycle suggest hormone receptor binding to chromatin may also be dynamic. Therefore, we employed a multi-faceted approach to examine in vivo dynamics of hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq for estrogen receptor alpha (ERα) and progesterone receptor (PGR). Genome wide, there were extensive estrous cycle dependent changes in ERα and PGR binding as well as chromatin accessibility. There were 4,159 differentially expressed genes between estrus and diestrus. At transcription start sites, accessibility generally correlated with the directionality of gene expression and there was reduced PGR in estrus compared to diestrus but little change in ERα. There were 2,727 enhancers with dynamic accessibility near these genes and 77% of those correlated with directionality of gene expression changes. However, most enhancers were constitutively open (8,694). In both dynamic and constitutively open enhancers, ERα and PgR binding was coordinately lost from diestrus to estrus. Diestrus specific ERα binding and accessible regions were enriched for PGR, FOX, GATA and SOX binding motifs. In contrast, estrus specific ERα binding occurred at transcription factor deserts in relatively closed chromatin while estrus specific accessible regions were highly enriched for ATF, ELF and ELK motifs. Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (RIME) revealed many estrous cycle dependent partners of ERα (diestrus, 60; estrus, 24). PGR was found in complex with ERα during diestrus but not estrus supporting coordinated binding of both receptors during diestrus. Two of the cohesin complex proteins, SMC1A and SMC3, were found in complex with ERα during diestrus but not estrus; overlap of SMC1A with ERα confirmed this preferential interaction during diestrus. Additionally, HiC analysis showed more diestrus specific interactions than estrus (476 versus 263) suggesting the SMC1A/ ERα interactions have functional consequences on chromatin structure. Taken together, a complex series of interactions between hormone receptors, chromatin structure and accessibility orchestrate estrous cycle dependent changes in gene expression.
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Project description:5-Fluorouracil (5-FU) is one of the most effective and widely used chemotherapeutic drugs in the treatment of colon cancer. Yet chemoresistance is a common feature of colon cancer, resulting in poor prognosis and short survival. Dynamic reprogramming of chromatin accessibility allows rapid access of the gene regulatory machinery to open genomic regions facilitating subsequent gene expression via direct transcription factor activation and regulatory element-binding. To better understand the regulatory network underlying 5-FU resistance in colon cancer cells, we explored the systematic alterations of chromatin accessibility and transcript expression by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with transcriptome sequencing, followed by integrative analysis to identify potential regulators and their targets associated with differentially accessible regions (DARs) in 5-FU-resistant HCT15 (HCT15-FR) cells. A total of 3175 differentially expressed mRNAs (DEGs), lncRNAs (DELs) and miRNAs (DEMs) related to 5-FU resistance were identified, including dramatically up-regulated IL33, H19, miR-17-5p, significantly down-regulated AKR1B10, LINC01012, miR-125b-5p, and potential chromatin modifiers such as INO80C, HDAC6 and KDM5A. A competitive endogenous RNAs (ceRNAs) regulatory network was established based on information about interactions among DEGs, DELs and DEMs, suggesting that H19, HOXA11-AS and NEAT1 might function as ceRNAs associate with 5-FU resistance in HCT15 cells. By integrating with transcriptome data, 9868 DARs were identified in HCT15-FR cells compared to control, which were positively (r = 0.58) correlated with their nearest DEGs and DELs. The up-regulated genes related to 4937 increased chromatin-accessible regions were significantly enriched in signaling pathways of MAPK, FOX and WNT, while the 4931 decreased chromatin-accessible regions were considered to be involved in declined biosynthesis of amino acids and nucleotide sugars, signaling pathways of Notch, and HIF-1. Analyses of the DAR sequences revealed that, besides AP-1 family, the TF DNA-binding motifs of FOX and KLF family members were highly enriched in hyper- and hypo-accessible regions, respectively. Moreover, relationships of critical TFs and their potential targets associated with DARs were identified, such as FOXA1, RUNX2, KLF3 and GRHL2. These data provided clear insights and valuable resources for an improved understanding of the non-genetic landscape of 5-FU-resistant colon cancer cells based on chromatin accessibility and transcript levels, which allowed for genome-wide detection of TF-binding sites, potential cis-regulatory elements and therapeutic targets.
2021-12-17 | GSE190951 | GEO
Project description:Stomata are pores in the epidermis of plants that can open and close, allowing for gas exchange with the environment, vital for photosynthesis, and regulating transpiration. They are formed from protodermal cells by a series of asymmetric and symmetric divisions and differentiation steps. Initiation into and progression within the stomatal lineage are driven by the consecutive expression and action of three sets of bHLH transcription factor dimers (SPCH, MUTE, FAMA plus their heterodimer partners SCRM or SCRM2) and is accompanied by massive changes in the transcriptome as well as the chromatin landscape. Strong shifts in chromatin accessibility have been observed specifically at the initiation stage and at the transition from division to differentiation. In line with this, FAMA, which promotes the differentiation of stomata, has been shown to interact with RBR, which can recruit the repressive PRC2 complex, to shut down the early stomatal lineage transcriptional program. Interestingly, several of the stomatal lineage bHLHs bind chromatin regions that are closed/inaccessible in a primordial state (the shoot apical meristem). This suggests that the stomatal lineage bHLHs could be able to access closed chromatin and that they might also be directly involved in opening (and closing) of chromatin at a subset of their target regions. In order to test this hypothesis and identify chromatin modifiers that associate with the stomatal lineage bHLH dimers, we did proximity labeling with TurboID fused to SCRM, which is expressed throughout the stomatal lineage and is the main heterodimerization partner of SPCH, MUTE and FAMA. We identified a number of proteins acting as chromatin modifiers and remodelers, including the histone acetyl transferase HAC1, which deposits activating marks on nucleosomes, and multiple subunits of the ATPase-dependent chromatin remodeling SWI/SNF complex. Together, these data support a role of SCRM and its partners in regulating target gene accessibility to impose lasting changes in gene expression within the stomatal lineage.
2024-06-14 | PXD040690 | Pride
Project description:ATAC-seq identified a total 80,764 peaks in radioresistant cells (HSC-3;0Gy, 8Gy) and radiosensitive cells (KOSC-2;0Gy, 8Gy) (n=2). 1273 peaks were shown as chromatin opened regions and 839 peaks were shown as chromatin closed regions in HSC-3 8Gy compared to HSC-3 0Gy. 285 peaks were shown as chromatin opened regions and 1760 peaks were shown as chromatin closed regions in KOSC-2 8Gy compared to KOSC-2 0Gy. 3804 peaks were shown as chromatin opened regions and 1929 peaks were shown as chromatin closed regions in KOSC-2 0Gy compared to HSC-3 0Gy. By hierarchical clustering analysis and heatmap, the difference of chromatin accessibility in KOSC-2 was lower than HSC-3.
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