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

GSE309861 Homo sapiens (human) Other 10 samples Submitted 2025/11/19 Platform GPL30173
At a glance

human · 10 samples

Organism
Homo sapiens (human)
Topic
Pancreatic cancerThis series is part of our curated briefing on it.
Samples
10 samples: 5 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI.
Summary (written by the submitters)
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.
Read the full summary ↓
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.
This dataset
Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE309861_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Also filed as BioProject PRJNA1283515. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly in duplicate
HiChIP_BxPC3 ×2 HiChIP_CFPAC1 ×2 HiChIP_HPAFII ×2 HiChIP_TCCPAN2 ×2 HiChIP_T3M4 ×2

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 10 sample titles; they account for 10 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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