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Kidney Week

Abstract: FR-PO354

Genome-Wide Identification of Active Enhancers in Renal Aging

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Oguchi, Akiko, RIKEN, Yokohama city, Japan
  • Yanagita, Motoko, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Murakawa, Yaushiro, RIKEN, Yokohama city, Japan
Background

Aging is one of the major risk factors for acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose people to renal diseases. However, the regulatory circuitry governing the transcriptional network in renal aging is unclear. Here we aim to reveal specific transcriptional programs that underlie renal aging. In particular, enhancers are distal non-codingDNA elements that are crucial for spatiotemporal control of gene expression. Disease-associated SNPs are highly enriched within enhancers, highlighting the functionality. Bidirectional RNA transcription (referred to as eRNA) originates from enhancers.

Methods

The CAGE (Cap Analysis of Gene Expression) is a method used to comprehensively map transcription start sites (TSSs) using next-generation sequencing. Using CAGE, promoters and enhancers can be identified by analyzing TSSs of mRNAs and eRNAs, respectively. However, in the usual CAGE method, detection of eRNAs is inefficient, because these transcripts are actively degraded in the nucleus by the nuclear exosome complex soon after their synthesis. To overcome this issue, our group devised a simple and novel NET-CAGE technology, in which nascent RNA is used as input. We successfully achieved ultra-sensitive detection and quantification of active enhancers at single nucleotide resolution.

Results

We apply this NET-CAGE technology to describe active cis-regulatory landscape across renal aging and analyze differentially regulated enhancers and genes. NET-CAGE data for kidney show increased detection of enhancers in each age compared to CAGE data. In addition, we identify a number of kidney-specific enhancers.

Conclusion

Our comprehensiveanalysis of enhancers will provide key biological insights into cis-regulatory mechanism in renal aging.