Chromatin accessibility of kidney tubular cells under stress reveals key transcription factor mediating acute and chronic kidney disease

FEBS J. 2021 Sep;288(18):5446-5458. doi: 10.1111/febs.15818. Epub 2021 Mar 29.

Abstract

Cellular injury caused by stimuli plays an important role in the progression of various diseases including acute and chronic kidney diseases. The dynamic transcriptional regulation responding to stimuli underlies the important mechanism of injury. In this study, we investigated the regulatory elements and their dynamic activities in kidney tubular epithelial cells. We captured the chromatin accessibility and gene expression with ATAC-seq and RNA sequencing under a variety of extracellular stimuli including H2 O2 , TGF-β1, and FG4592 which is an agonist of hypoxia-inducible factor. Our results revealed both condition-specific and condition-shared transcription regulation. Interestingly, the shared regulation program revealed that the key transcription factor HNF1B-mediated cellular reprogramming leads to a common change among the stimuli. We found the HNF1B regulatory network was significantly disrupted in various kidney diseases.

Keywords: HNF1B; chromatin accessibility; kidney disease; renal tubule; transcription reprogramming under stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Chromatin / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / genetics
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hypoxia-Inducible Factor 1 / agonists
  • Hypoxia-Inducible Factor 1 / genetics
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / pathology
  • Transcription Factors / genetics
  • Transforming Growth Factor beta1 / genetics

Substances

  • Chromatin
  • HNF1B protein, human
  • Hypoxia-Inducible Factor 1
  • TGFB1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1
  • Hepatocyte Nuclear Factor 1-beta
  • Hydrogen Peroxide