Toggle navigation
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
Search ...
Go!
DIO2 gene expression is stimulated by EBF2 and repressed by ZNF423
Stable Identifier
R-HSA-9844598
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
,
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Developmental Biology (Homo sapiens)
Adipogenesis (Homo sapiens)
Transcriptional regulation of brown and beige adipocyte differentiation (Homo sapiens)
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 (Homo sapiens)
DIO2 gene expression is stimulated by EBF2 and repressed by ZNF423 (Homo sapiens)
General
SBML
|
BioPAX
Level 2
Level 3
|
PDF
SVG
|
PNG
Low
Medium
High
|
PPTX
|
SBGN
Click the image above or
here
to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
DIO2 gene encodes type II iodothyronine deiodinase, which is essential for adaptive thermogenesis in brown adipose tissue, as one of the regulators of the adaptive thermogenesis is the thyroid hormone T3 (3,5,3’-triiodothyronine). Based entirely on different mouse studies cited below DIO2 gene is annotated as a candidate EBF2 target gene, as direct binding of EBF2 to the regulatory regions of this gene has not been reported. EBF2 promotes DIO2 gene expression in white adipocytes during their transition to beige adipocytes (Rajakumari et al. 2013), while knockdown of EBF2 mRNA in beige adipocytes leads to downregulation of DIO2 (Pearson et al. 2019). Upregulation of Blnc1, a lncRNA that interacts with the transcription factor EBF2 and stimulates EBF2-mediated induction of gene involved in beige and brown adipogenesis, is associated with upregulation of DIO2 mRNA expression (Zhao et al. 2014; Mi et al. 2017). Depletion of DPF3, a subunit of the BAF chromatin remodeling complex that binds EBF2 and promotes transcription of EBF2 target genes, leads to downregulation of DIO2 mRNA (Shapira et al. 2017). Ectopic overexpression of ID1, which was reported to bind to and negatively regulate EBF2, leads to reduced DIO2 expression (Patil et al. 2017). ZNF423, an inhibitor of EBF2 transcriptional activity, represses DIO2 gene expression (Shao et al. 2016; Shao et al. 2021) and the repression is dependent on the ability of ZNF423 to interact with the NuRD transcriptional repressor complex (Shao et al. 2021).
Participants
Input
DIO2 gene [nucleoplasm]
(Homo sapiens)
Output
DIO2 [plasma membrane]
(Homo sapiens)
Participates
as an event of
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 (Homo sapiens)
This event is regulated
Negatively by
Regulator
NuRD complex [nucleoplasm]
(Homo sapiens)
Active Unit
NuRD complex [nucleoplasm]
Regulator
ZNF423 [nucleoplasm]
(Homo sapiens)
Active Unit
ZNF423 [nucleoplasm]
Positively by
Regulator
EBF2,EBF2:Blnc1 lncRNA:HNRNPU [nucleoplasm]
(Homo sapiens)
Active Unit
EBF2,EBF2:Blnc1 lncRNA:HNRNPU [nucleoplasm]
Inferred From
Dio2 gene expression is stimulated by Ebf2 and repressed by Znf423 and NuRD (Mus musculus)
Authored
Orlic-Milacic, M (2023-09-25)
Reviewed
Chun, TH (2023-11-29)
Created
Orlic-Milacic, M (2023-09-21)
© 2025
Reactome
Cite Us!
Cite Us!
Cite Us!
Warning!
Unable to extract citation. Please try again later.
Download As:
BibTeX
RIS
Text