PUBLICATION
A permissive epigenetic landscape facilitates distinct transcriptional signatures of activating transcription factor 6 in the liver
- Authors
- Nair, A.R., Lakhiani, P., Zhang, C., Macchi, F., Sadler, K.C.
- ID
- ZDB-PUB-211207-7
- Date
- 2021
- Source
- Genomics 114(1): 107-124 (Journal)
- Registered Authors
- Macchi, Filippo, Sadler Edepli, Kirsten C., Zhang, Chi
- Keywords
- ATF6, Chromatin, Epigenome, Liver, Unfolded Protein response
- Datasets
- GEO:GSE130800, GEO:GSE151291, GEO:GSE130801
- MeSH Terms
-
- Activating Transcription Factor 6*/genetics
- Activating Transcription Factor 6*/metabolism
- Animals
- Epigenesis, Genetic*
- Liver/metabolism
- Mice
- Unfolded Protein Response
- Zebrafish*/genetics
- PubMed
- 34863900 Full text @ Genomics
Citation
Nair, A.R., Lakhiani, P., Zhang, C., Macchi, F., Sadler, K.C. (2021) A permissive epigenetic landscape facilitates distinct transcriptional signatures of activating transcription factor 6 in the liver. Genomics. 114(1):107-124.
Abstract
Restoring homeostasis following proteostatic stress hinges on a stress-specific transcriptional signature. How these signatures are regulated is unknown. We use functional genomics to uncover how activating transcription factor 6 (ATF6), a central factor in the unfolded protein response, regulates its target genes in response to toxicant induced and physiological stress in the liver. We identified 652 conserved putative ATF6 targets (CPATs), which functioned in metabolism, development and proteostasis. Strikingly, Atf6 activation in the zebrafish liver by transgenic nAtf6 overexpression, ethanol and arsenic exposure resulted in a distinct CPAT signature for each; with only 34 CPATs differentially expressed in all conditions. In contrast, during liver regeneration in mice resulted in a dynamic differential expression pattern of 53% of CPATs. These CPATs were distinguished by residing in open chromatin, H3K4me3 occupancy and the absence of H3K27me3 on their promoters. This suggests that a permissive epigenetic landscape allows stress-specific Atf6 target gene expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping