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The Farnesoid-X-Receptor activates transcription independently of RXR at non-canonical response elements

GSE261662 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2024/11/18 Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
30 samples: 30 samples, each with a distinct title — no replicated groupsGroups 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; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
The farnesoid X receptor activates transcription independently of RXR at non-canonical response elementsNucleic acids research · 2025
Summary (written by the submitters)
The Farnesoid-X-Receptor (FXR) is a nuclear receptor (NR) known to obligately heterodimerize with Retinoid-X-Receptor (RXR). FXR is expressed as four isoforms (α1-α4) that drive transcription from IR-1 (inverted repeat-1) DNA motifs. More recently, FXR isoforms α2/α4 were found to activate transcription predominantly from non-canonical ER-2 (everted repeat-2) DNA motifs, mediating most metabolic effects of general FXR activation.
Read the full summary ↓
Here, we explored molecular determinants of FXRα2 regulation from ER-2 elements through quantitative interaction proteomics, site-directed mutagenesis, and transcriptomics. We discovered that FXRα2 binds to and activates ER-2 elements in vitro and in reporter assays independently of RXR. Genome-wide analysis in mouse liver revealed higher ER-2 motif enrichment in RXR-lacking FXR binding sites. Abrogation of FXRα2:RXR heterodimerization abolished IR-1, but preserved ER-2 transactivation. Transcriptome-wide, RXR overexpression inhibited 25% of FXRα2 targets in HepG2. These genes were specifically activated by the heterodimerization-deficient mutant FXRα2-L434R, were enriched for ER-2 motifs at their promoters and were involved in lipid metabolism and ammonia detoxification. In conclusion, RXR acts as a molecular switch, promoting FXRα2 activation from IR-1 instead of ER-2 motifs. Our results showcase FXR as the first NR with RXR-dependent and independent modes of activation, highlighting a potential new layer of complexity for other RXR-heterodimerizing NRs.
Published in
The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements
van der Veen SW, Dijkstra JJ, Willemsen ECL et al. · Nucleic acids research 2025 · PMID 39657775 · doi:10.1093/nar/gkae1214
This dataset
Open GSE261662 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, 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.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE261662_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1088179 and SRA study SRP495337. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39657775) ↗
Study design
30 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 30 sample titles: 30 distinct titles with little repetition. 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
Datasets on a similar topic

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