Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KLF5 modulates epigenetic modifications driving human pancreatic ductal adenocarcinoma metastasis [RNA-Seq]

ABSTRACT: We previously showed that distant metastases of human pancreatic ductal adenocarcinoma (PDAC) are driven by epigenetic alterations in the primary tumor rather than by additional mutations1. However, the specific epigenetic driver genes responsible have not been identified. To identify genes modulating these changes, we performed a pooled CRISPR genetic screen and single-cell multiomics analysis using patient-derived xenograft cell lines established from a primary PDAC tumor and a distant metastasis from the same patient. We identified KLF5 as the leading epigenetic modulator regulating progression in distant metastasis. Knockdown of KLF5 selectively reduced the growth of the distant metastasis and caused a large-scale increase in heterochromatin. Single-cell multiome ATAC and gene expression analysis revealed two clusters with high KLF5 expression and increased expression and chromatin accessibility of stem cell markers and genes related to migration and epithelial to mesenchymal transition. Further, we identified two epigenetic modifiers, NCAPD2 and MTHFD1, which are regulated by KLF5 and result in these increases in heterochromatin when knocked down. These data provide a sequence of epigenetic modulators, modifiers and mediators which shape the metastatic landscape of pancreatic cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290273 | GEO | 2026/02/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

KLF5 modulates epigenetic modifications driving human pancreatic ductal adenocarcinoma metastasis [Multiome]

Project description:We previously showed that distant metastases of human pancreatic ductal adenocarcinoma (PDAC) are driven by epigenetic alterations in the primary tumor rather than by additional mutations1. However, the specific epigenetic driver genes responsible have not been identified. To identify genes modulating these changes, we performed a pooled CRISPR genetic screen and single-cell multiomics analysis using patient-derived xenograft cell lines established from a primary PDAC tumor and a distant metastasis from the same patient. We identified KLF5 as the leading epigenetic modulator regulating progression in distant metastasis. Knockdown of KLF5 selectively reduced the growth of the distant metastasis and caused a large-scale increase in heterochromatin. Single-cell multiome ATAC and gene expression analysis revealed two clusters with high KLF5 expression and increased expression and chromatin accessibility of stem cell markers and genes related to migration and epithelial to mesenchymal transition. Further, we identified two epigenetic modifiers, NCAPD2 and MTHFD1, which are regulated by KLF5 and result in these increases in heterochromatin when knocked down. These data provide a sequence of epigenetic modulators, modifiers and mediators which shape the metastatic landscape of pancreatic cancer.

2026-02-10 | GSE290274 | GEO

KLF5 co-immunoprecipitation mass spectrometry

Project description:Lineage plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor heterogeneity and therapeutic resistance. Here, we identify KLF5 as a dynamic master regulator of epithelial lineage identity in PDAC, with dichotomous roles in promoting either classical or basal-like transcriptional programs. Through unbiased proteomic and genetic screens, we uncover the AAA+ ATPases RUVBL1 and RUVBL2 as essential coactivators of KLF5 across both lineage states. We demonstrate that ATP hydrolysis by RUVBL1/2 is required for the stable interaction with an intrinsically disordered region of KLF5, enabling its recruitment to lineage-specific enhancers and driving transcriptional regulation of identity-defining genes. Notably, small-molecule inhibitors of RUVBL1/2 ATPase activity, which have anti-PDAC activity in vivo, suppress KLF5-dependent transcription. These findings define a previously unrecognized mechanism of ATP hydrolysis-dependent transcriptional coactivation by AAA+ ATPases and highlight a potential therapeutic strategy for modulating aberrant lineage programs in cancer. This project contains files relative to a Co-IP MS with KLF5-MBP as bait.

2025-08-21 | PXD066112 | Pride

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous and contain both subtypes. Therefore, therapeutic approaches targeting only one subtype are unlikely to be effective as standalone PDAC treatments. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors.

2025-11-25 | GSE310807 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [HiChIPseq]

2025-11-19 | GSE309861 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [ChIPseq]

2025-11-19 | GSE309860 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [EU-RNAseq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous contain of both subtypes. Therefore, therapeutic approaches targeting one subtype may not be suitable for PDAC therapy. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors.

2025-07-01 | GSE301285 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [ChIP-Seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous contain of both subtypes. Therefore, therapeutic approaches targeting one subtype may not be suitable for PDAC therapy. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors.

2025-07-01 | GSE301284 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [RNA-Seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous contain of both subtypes. Therefore, therapeutic approaches targeting one subtype may not be suitable for PDAC therapy. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors.

2025-07-01 | GSE301283 | GEO

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival [ATAC-seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous contain of both subtypes. Therefore, therapeutic approaches targeting one subtype may not be suitable for PDAC therapy. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors.

2025-07-01 | GSE301272 | GEO

KLF5 regulates actin remodeling to enhance the metastasis of nasopharyngeal carcinoma [RNA-seq]

Project description:Transcription factors (TFs) engage in various cellular essential processes including differentiation, growth and migration. However, the master TF involved in distant metastasis of nasopharyngeal carcinoma (NPC) remains largely unclear. Here we show that KLF5 regulates actin remodeling to enhance NPC metastasis. We analyzed the msVIPER algorithm-generated transcriptional regulatory networks and identified KLF5 as a master TF of metastatic NPC linked to poor clinical outcomes. KLF5 regulates actin remodeling and lamellipodia formation to promote the metastasis of NPC cells in vitro and in vivo. Mechanistically, KLF5 preferentially occupies distal enhancer regions of ACTN4 to activate its transcription, whereby decoding the informative DNA sequences. ACTN4, extensively localized within actin cytoskeleton, facilitates dense and branched actin networks and lamellipodia formation at the cell leading edge, empowering cells to migrate faster. Collectively, our findings reveal that KLF5 controls robust transcription program of ACTN4 to modulate actin remodeling and augment cell motility which enhances NPC metastasis, and provide new potential biomarkers and therapeutic interventions for NPC.

2024-04-18 | GSE243952 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data