Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury.
Acute Kidney Injury
/ genetics
Amino Acid Motifs
Animals
Binding Sites
Cell Proliferation
Enhancer Elements, Genetic
Epigenesis, Genetic
Fibrosis
Hepatocyte Nuclear Factor 4
/ metabolism
Kidney
/ metabolism
Kidney Tubules
/ cytology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nuclear Proteins
Receptors, Glucocorticoid
/ metabolism
Regulatory Elements, Transcriptional
Reperfusion Injury
/ metabolism
STAT3 Transcription Factor
/ metabolism
STAT5 Transcription Factor
/ metabolism
Signal Transduction
Transcription Factors
Transcription, Genetic
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 07 2020
07 07 2020
Historique:
received:
08
04
2019
accepted:
09
06
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
9
9
2020
Statut:
epublish
Résumé
The endogenous repair process can result in recovery after acute kidney injury (AKI) with adaptive proliferation of tubular epithelial cells, but repair can also lead to fibrosis and progressive kidney disease. There is currently limited knowledge about transcriptional regulators regulating these repair programs. Herein we establish the enhancer and super-enhancer landscape after AKI by ChIP-seq in uninjured and repairing kidneys on day two after ischemia reperfusion injury (IRI). We identify key transcription factors including HNF4A, GR, STAT3 and STAT5, which show specific binding at enhancer and super-enhancer sites, revealing enhancer dynamics and transcriptional changes during kidney repair. Loss of bromodomain-containing protein 4 function before IRI leads to impaired recovery after AKI and increased mortality. Our comprehensive analysis of epigenetic changes after kidney injury in vivo has the potential to identify targets for therapeutic intervention. Importantly, our data also call attention to potential caveats involved in use of BET inhibitors in patients at risk for AKI.
Identifiants
pubmed: 32636391
doi: 10.1038/s41467-020-17205-5
pii: 10.1038/s41467-020-17205-5
pmc: PMC7341735
doi:
Substances chimiques
Brd4 protein, mouse
0
Hepatocyte Nuclear Factor 4
0
Hnf4a protein, mouse
0
Nuclear Proteins
0
Receptors, Glucocorticoid
0
STAT3 Transcription Factor
0
STAT5 Transcription Factor
0
Stat3 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3383Subventions
Organisme : NIDDK NIH HHS
ID : R37 DK039773
Pays : United States
Organisme : NCATS NIH HHS
ID : UH3 TR002155
Pays : United States
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