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Renin Regulatory Pathway Inhibition Epigenetically Silences *Ren1* (CUTnTag)

GSE254943 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 13 samples Submitted 2024/08/26 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 13 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
13 samples: 6 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; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised StateHypertension (Dallas, Tex. : 1979) · 2024
Summary (written by the submitters)
Background: Renin-expressing cells are myoendocrine cells crucial for survival which detect changes in blood pressure and release renin to maintain homeostasis. Renin is regulated through several pathways including cAMP, p300/CBP, and BET proteins including Brd4. Binding to the cAMP-responsive element in the renin enhancer region amplifies renin transcription and relies on each of these factors for an appropriate response.
Read the full summary ↓
The specific regulatory changes that occur following inhibition of these pathways remains understudied. Therefore, we aimed to evaluate chromatin changes and gene signatures that occur following inhibition of renin regulatory factors. Methods: We treated As4.1 cells (a tumoral cell line that constitutively expresses renin) with three inhibitors (H89: PKA inhibition; JQ1: Brd4 inhibition; A-485: p300/CBP inhibition) that target required factors for renin transcriptional regulation. We then performed ATAC-seq, scRNA-seq, and ChIP-seq for H3K27ac and P300 binding on biological replicates of treated and control As4.1 cells. Results: Ren1 expression is significantly, but transiently, reduced following each inhibitory treatment. Further, PKA inhibition leads to corresponding losses in H3K27ac and p300 binding at the locus. A restricted set of nine genes with overlapping dynamically accessible regions, differential gene expression, and H3K27ac and p300 binding were identified with roles across three primary renin regulatory paradigms. Conclusions: The data shows that renin expression is regulated through a switch from an active to poised state of epigenetic control, a shift toward a less differentiated cellular identity via the loss of enhancer elements, and the disruption of cAMP, baroreceptor, and Notch mediated renin regulatory pathways.
Published in
Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State
Smith JP, Paxton R, Medrano S et al. · Hypertension (Dallas, Tex. : 1979) 2024 · PMID 38989586 · doi:10.1161/HYPERTENSIONAHA.124.22886
This dataset
Open GSE254943 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE254943_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1072678 and SRA study SRP487795. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38989586) ↗
Study design
6 conditions, mostly in duplicate
As4.1 cells, H3K4me1, ×2 As4.1 cells, H3K4me3, ×2 As4.1 cells, H2BK5ac, ×2 As4.1 cells, H4K16ac, ×2 As4.1 cells, H4K5ac, ×2 As4.1 cells, H3K27ac, ×2 As4.1 cells, IgG ×1

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 13 sample titles; they account for 12 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
Datasets on a similar topic

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