Ucp1 gene expression is stimulated by Ebf2 and Pparg and repressed by Znf423 and NuRD

Stable Identifier
R-MMU-9844554
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm, mitochondrial inner membrane
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Ucp1 gene expression is stimulated by Ebf2 and Pparg and repressed by Znf423 and NuRD
In mouse brown adipocyte lineage Ucp1 gene is directly transcriptionally regulated by Ebf2 transcription factor which binds to regulatory elements of the Ucp1 gene to activate Ucp1 gene transcription (Rajakumari et al. 2013; Wang et al. 2014; Shao et al. 2014; Shao et al. 2021). Ebf2 facilitates recruitment of the Pparg:Rxra transcription factor complex to the PPREs (peroxisome proliferator response elements) in the vicinity of Ebf binding sites at the Ucp1 gene locus. Pparg augments Ucp1 gene transcription synergistically with Ebf2 (Rajakumari et al. 2013; Shao et al. 2021). Ebf2-mediated recruitment of the BAF complex to regulatory sequences in the Ucp1 gene locus may precede Ebf2-facilitated binding of Pparg to the Ucp1 gene locus (Shao et al. 2021). During differentiation of beige adipocytes in mouse inguinal white adipose tissue Ebf2 and Pparg synergistically upregulate Ucp1 mRNA levels (Stine et al. 2016). 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 Ucp1 mRNA (Shapira et al. 2017). Blnc1 lncRNA, a cofactor of Ebf2, significantly increases binding of Ebf2 to the Ucp1 gene locus and Ebf2-mediated transcriptional activation of Ucp1 (Zhao et al. 2014; Mi et al. 2017). Mll4 histone methyltransferase complex is required for the formation of the super-enhancer at the Ucp1 gene locus (Lai et al. 2017). Ucp1 gene expression is negatively regulated by Znf423-mediated inhibition of Ebf2 transcriptional activity, which is associated with the recruitment of the NuRD complex to the Ucp1 gene regulatory sequences (Shao et al. 2021).
Literature References
PubMed ID Title Journal Year
25002143 A long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation

Zhao, XY, Li, S, Wang, GX, Yu, Q, Lin, JD

Mol Cell 2014
34620682 ZFP423 controls EBF2 coactivator recruitment and PPARĪ³ occupancy to determine the thermogenic plasticity of adipocytes

Shao, M, Zhang, Q, Truong, A, Shan, B, Vishvanath, L, Li, L, Seale, P, Gupta, RK

Genes Dev 2021
28398509 MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis

Lai, B, Lee, JE, Jang, Y, Wang, L, Peng, W, Ge, K

Nucleic Acids Res 2017
28428261 EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex

Shapira, SN, Lim, HW, Rajakumari, S, Sakers, AP, Ishibashi, J, Harms, MJ, Won, KJ, Seale, P

Genes Dev 2017
28123941 Conserved function of the long noncoding RNA Blnc1 in brown adipocyte differentiation

Mi, L, Zhao, XY, Li, S, Yang, G, Lin, JD

Mol Metab 2017
25197048 Ebf2 is a selective marker of brown and beige adipogenic precursor cells

Wang, W, Kissig, M, Rajakumari, S, Huang, L, Lim, HW, Won, KJ, Seale, P

Proc Natl Acad Sci U S A 2014
23499423 EBF2 determines and maintains brown adipocyte identity

Rajakumari, S, Wu, J, Ishibashi, J, Lim, HW, Giang, AH, Won, KJ, Reed, RR, Seale, P

Cell Metab 2013
26844207 EBF2 promotes the recruitment of beige adipocytes in white adipose tissue

Stine, RR, Shapira, SN, Lim, HW, Ishibashi, J, Harms, M, Won, KJ, Seale, P

Mol Metab 2016
27238639 Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program

Shao, M, Ishibashi, J, Kusminski, CM, Wang, QA, Hepler, C, Vishvanath, L, MacPherson, KA, Spurgin, SB, Sun, K, Holland, WL, Seale, P, Gupta, RK

Cell Metab 2016
Participants
Input
Output
This event is regulated
Negatively by
Regulator
NuRD:Znf423:Ebf2,Ebf2:Blnc1 lncRNA:Hnrnpu:Ucp1 gene [nucleoplasm] (Mus musculus)
Active Unit
mNuRD complex [nucleoplasm]
Znf423 [nucleoplasm]
Positively by
Regulator
Ebf2, Ebf2:Blnc1 lncRNA:Hnrnpu, Activated Pparg:Rxra:Ucp1 gene [nucleoplasm] (Mus musculus)
Active Unit
Ebf2, Ebf2:Blnc1 lncRNA:Hnrnpu [nucleoplasm]
Activated Pparg:Rxra [nucleoplasm]
Orthologous Events
UCP1 gene expression is stimulated by EBF2 and PPARG and repressed by ZNF423 and NuRD (Homo sapiens)
Authored
Orlic-Milacic, M  (2023-09-25)
Reviewed
Chun, TH  (2023-12-01)
Created
Orlic-Milacic, M  (2023-09-19)
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