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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 26, 2024 |
| Title |
Renin Regulatory Pathway Inhibition Epigenetically Silences *Ren1* (ChIP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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. 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.
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| Overall design |
The regulation of renin was evaluated in As4.1 cells, a mouse cell line which expresses high levels of renin mRNA, by treating with either a control compound (DMSO) or separate inhibitors to either PKA, Brd4, or p300/CBP. The regulatory effects were evaluated using ATAC-seq, scRNA-seq, and ChIP-seq for H3K27ac and P300 binding.
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| Contributor(s) |
Smith JP, Paxton R, Medrano S, Sheffield NC, Sequeira-Lopez MS, Gomez RA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 02, 2024 |
| Last update date |
Aug 26, 2024 |
| Contact name |
Jason Paul Smith |
| E-mail(s) |
jasonsmith@virginia.edu
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| Phone |
9193455043
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| Organization name |
University of Virginia
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| Department |
Pediatrics
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| Lab |
Gomez Sequeira-Lopez
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| Street address |
409 Lane Rd
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22903 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| GSM8060491 |
As4.1 cells, H89, H3K27ac, rep2 |
| GSM8060492 |
As4.1 cells, DMSO, p300, rep1 |
| GSM8060493 |
As4.1 cells, DMSO, p300, rep2 |
| GSM8060494 |
As4.1 cells, H89, p300, rep1 |
| GSM8060495 |
As4.1 cells, H89, p300, rep2 |
| GSM8060496 |
As4.1 cells, Input |
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| This SubSeries is part of SuperSeries: |
| GSE254945 |
Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State |
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| Relations |
| BioProject |
PRJNA1072669 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE254941_As4.1_DMSO-v-H89_H3K27Ac_DMSO_enriched_peaks.bed.gz |
61.5 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_DMSO-v-H89_H3K27Ac_H89_enriched_peaks.bed.gz |
155.4 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_DMSO-v-H89_H3K27Ac_consensus_peaks.bed.gz |
389.6 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_DMSO-v-H89_P300_DMSO_enriched_peaks.bed.gz |
8.2 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_DMSO-v-H89_P300_H89_enriched_peaks.bed.gz |
19.0 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_DMSO-v-H89_P300_consensus_peaks.bed.gz |
452.7 Kb |
(ftp)(http) |
BED |
| GSE254941_As4.1_H3K27Ac_DMSO.bigWig |
236.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE254941_As4.1_H3K27Ac_H89.bigWig |
197.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE254941_As4.1_P300_DMSO.bigWig |
287.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE254941_As4.1_P300_H89.bigWig |
301.8 Mb |
(ftp)(http) |
BIGWIG |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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