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Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation
by
Zhu, Liangru
, Li, Jiamin
, Zhang, Xiaopeng
, Li, Junrong
, Yu, Qi
, Liu, Fang
, Chen, Yidong
in
Activating Transcription Factors - genetics
/ Activating Transcription Factors - metabolism
/ Analysis
/ Animals
/ ATF7
/ Autophagy
/ Biopsy
/ Chromatin
/ Colitis - chemically induced
/ Colitis - genetics
/ Colitis - metabolism
/ Colitis - pathology
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - pathology
/ Colon - metabolism
/ Colon - pathology
/ Dextran
/ Dextran Sulfate
/ Diarrhea
/ Disease
/ Epigenomics - methods
/ Epithelial cells
/ Epithelial Cells - metabolism
/ Epithelial Cells - pathology
/ Epithelium
/ Ethylenediaminetetraacetic acid
/ Genomes
/ Homeostasis
/ Humans
/ Immunoprecipitation
/ Inflammation
/ Inflammation - genetics
/ Inflammation - pathology
/ Inflammatory bowel disease
/ Inflammatory bowel diseases
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Luciferase
/ Membrane potential
/ Membrane Potential, Mitochondrial - genetics
/ Metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitophagy
/ Mitophagy - genetics
/ Oxidative stress
/ Pathogenesis
/ PINK1
/ Promoter Regions, Genetic
/ Protein Kinases - genetics
/ Protein Kinases - metabolism
/ PTEN-induced putative kinase
/ Quality control
/ Quality management
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Roles
/ Signal Transduction
/ Transcription activation
/ Transcription factors
/ Transcriptomics
/ Ulcerative colitis
2025
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Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation
by
Zhu, Liangru
, Li, Jiamin
, Zhang, Xiaopeng
, Li, Junrong
, Yu, Qi
, Liu, Fang
, Chen, Yidong
in
Activating Transcription Factors - genetics
/ Activating Transcription Factors - metabolism
/ Analysis
/ Animals
/ ATF7
/ Autophagy
/ Biopsy
/ Chromatin
/ Colitis - chemically induced
/ Colitis - genetics
/ Colitis - metabolism
/ Colitis - pathology
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - pathology
/ Colon - metabolism
/ Colon - pathology
/ Dextran
/ Dextran Sulfate
/ Diarrhea
/ Disease
/ Epigenomics - methods
/ Epithelial cells
/ Epithelial Cells - metabolism
/ Epithelial Cells - pathology
/ Epithelium
/ Ethylenediaminetetraacetic acid
/ Genomes
/ Homeostasis
/ Humans
/ Immunoprecipitation
/ Inflammation
/ Inflammation - genetics
/ Inflammation - pathology
/ Inflammatory bowel disease
/ Inflammatory bowel diseases
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Luciferase
/ Membrane potential
/ Membrane Potential, Mitochondrial - genetics
/ Metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitophagy
/ Mitophagy - genetics
/ Oxidative stress
/ Pathogenesis
/ PINK1
/ Promoter Regions, Genetic
/ Protein Kinases - genetics
/ Protein Kinases - metabolism
/ PTEN-induced putative kinase
/ Quality control
/ Quality management
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Roles
/ Signal Transduction
/ Transcription activation
/ Transcription factors
/ Transcriptomics
/ Ulcerative colitis
2025
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Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation
by
Zhu, Liangru
, Li, Jiamin
, Zhang, Xiaopeng
, Li, Junrong
, Yu, Qi
, Liu, Fang
, Chen, Yidong
in
Activating Transcription Factors - genetics
/ Activating Transcription Factors - metabolism
/ Analysis
/ Animals
/ ATF7
/ Autophagy
/ Biopsy
/ Chromatin
/ Colitis - chemically induced
/ Colitis - genetics
/ Colitis - metabolism
/ Colitis - pathology
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - pathology
/ Colon - metabolism
/ Colon - pathology
/ Dextran
/ Dextran Sulfate
/ Diarrhea
/ Disease
/ Epigenomics - methods
/ Epithelial cells
/ Epithelial Cells - metabolism
/ Epithelial Cells - pathology
/ Epithelium
/ Ethylenediaminetetraacetic acid
/ Genomes
/ Homeostasis
/ Humans
/ Immunoprecipitation
/ Inflammation
/ Inflammation - genetics
/ Inflammation - pathology
/ Inflammatory bowel disease
/ Inflammatory bowel diseases
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine
/ Luciferase
/ Membrane potential
/ Membrane Potential, Mitochondrial - genetics
/ Metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitophagy
/ Mitophagy - genetics
/ Oxidative stress
/ Pathogenesis
/ PINK1
/ Promoter Regions, Genetic
/ Protein Kinases - genetics
/ Protein Kinases - metabolism
/ PTEN-induced putative kinase
/ Quality control
/ Quality management
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Roles
/ Signal Transduction
/ Transcription activation
/ Transcription factors
/ Transcriptomics
/ Ulcerative colitis
2025
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Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation
Journal Article
Epigenomic Profiling Positions ATF7 as a Core Regulator of Colonic Inflammation
2025
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Overview
ABSTRACT
Mitochondrial dysfunction plays a central role in epithelial damage and persistent inflammation in ulcerative colitis (UC), but the transcriptional mechanisms that govern mitochondrial quality control in the intestinal epithelium remain poorly defined. Here, we identify Activating Transcription Factor 7 (ATF7) as a key regulator of mitophagy in colonic epithelial cells. Integrative transcriptomic and epigenomic analyses of patient‐derived mucosal samples revealed marked ATF7 downregulation and widespread activation of inflammatory pathways. Chromatin immunoprecipitation and luciferase reporter assays demonstrated that ATF7 directly binds to and activates the promoter of PINK1, a master regulator of mitophagy. Genetic ablation of ATF7 or PINK1 in human epithelial cells impaired mitophagy, disrupted mitochondrial membrane potential, and increased reactive oxygen species. In vivo, intestinal epithelial cell‐specific knockout of ATF7 or PINK1 exacerbated dextran sulfate sodium‐induced colitis, with greater epithelial injury, elevated cytokine production, and transcriptional activation of TNF, NF‐kappaB, and inflammatory bowel disease signalling pathways. These results establish ATF7 as a critical transcriptional regulator linking mitochondrial homeostasis to epithelial resilience in the inflamed colon.
Publisher
John Wiley & Sons, Inc
Subject
Activating Transcription Factors - genetics
/ Activating Transcription Factors - metabolism
/ Analysis
/ Animals
/ ATF7
/ Biopsy
/ Colitis - chemically induced
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - pathology
/ Dextran
/ Diarrhea
/ Disease
/ Epithelial Cells - metabolism
/ Epithelial Cells - pathology
/ Ethylenediaminetetraacetic acid
/ Genomes
/ Humans
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Membrane Potential, Mitochondrial - genetics
/ Mice
/ PINK1
/ Protein Kinases - metabolism
/ PTEN-induced putative kinase
/ Reactive Oxygen Species - metabolism
/ Roles
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