Abstract 066: Enhancer Repertoires That Define Renin Cell Identity
| Autor: | Mazhar Adli, Silvia Medrano, Allan Dickerman, Masafumi Oka, Maria Luisa S. Sequeira-Lopez, R. A. Gomez, Maria F Martinez, Ellen S. Pentz |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Hypertension. 68 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.68.suppl_1.066 |
| Popis: | Control of the renin cell phenotype is crucial for the regulation of blood pressure and fluid- electrolyte homeostasis. Enhancers are cis -acting DNA sequences that harbor distinct chromatin features and regulate gene expression in an orientation-independent manner. Recently, clusters of enhancers or super-enhancers (SE) highly enriched with master transcription factors, possessing open chromatin configuration and in close proximity to cell-identity genes have been proposed. We tested the hypothesis that renin cells have unique repertoires of enhancers and super-enhancers, distinct from other cell types. Those regulatory clusters may in turn confer the identity of renin cells. To define the genome-wide enhancer landscape characteristic of renin cells, we studied As4.1 cells, kidney tumor cells that express renin constitutively, and native renin cells sorted from the kidneys of Ren1cKO-YFP + mice. In these mice, the renin promoter drives YFP expression thus marking the renin cells. We used genome-wide ChIP-Seq for Med1 (subunit 1 of the Mediator complex), H3K27Ac (active enhancers) and Pol II (to visualize putative genomic areas undergoing transcription). The ROSE algorithm we used to ascertain super-enhancers. Chromatin accessibility genome-wide was assessed using ATAC-Seq. The results were compared to twenty-one other cell types that do not express renin. In As4.1 cells, we identified 14,871 enhancers based on H3K27Ac. Of those, 888 were classified as super-enhancers. The Med1 signal in As4.1 cells showed a SE localized 5kb upstream the Ren1 gene, which was ranked at position 25 among other SEs. The H3K27Ac signal showed highest occupancy in the same region. ChIP-Seq for H3K27Ac in YFP + cells showed 211 SEs of 2,987 peaks. The SE for the renin gene possessed the highest signal and ranked number 1, indicating its importance in renin cells. One hundred and thirteen SEs were unique to renin cells, including the SE associated with the renin gene. ATAC-Seq signals overlapped with the renin SE and the classical enhancer indicating that the chromatin was accessible for transcription. In summary, renin-expressing cells possess distinct repertoires of unique enhancers and super-enhancers that acting in concert are likely to determine the renin phenotype. |
| Databáze: | OpenAIRE |
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