Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

doi:10.1038/s41418-020-00714-7

. 2021 Jun;28(6):1880-1899.

doi: 10.1038/s41418-020-00714-7. Epub 2021 Jan 18.

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

Longmin Chen^#¹, Jing Zhang^#¹, Yuan Zou¹, Faxi Wang¹, Jingyi Li¹, Fei Sun¹, Xi Luo¹, Meng Zhang^{1

2}, Yanchao Guo^{1

2}, Qilin Yu¹, Ping Yang¹, Qing Zhou¹, Zhishui Chen^{1

3}, Huilan Zhang¹, Quan Gong⁴, Jiajun Zhao⁵, Decio L Eizirik⁶, Zhiguang Zhou⁷, Fei Xiong⁸, Shu Zhang⁹, Cong-Yi Wang¹⁰

Affiliations

¹ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Nephrology,Tongji Hospital, Tongji College of Medicine, Huazhong University of Science and Technology, Wuhan, China.
³ Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Tongji Hospital, Wuhan, China.
⁴ Clinical Molecular Immunology Center, Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China.
⁵ Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁶ ULB Center for Diabetes Research, Université Libre de Bruxelles, 808 Route de Lennik, B-1070, Brussels, Belgium.
⁷ Diabetes Center, The Second Xiangya Hospital, Institute of Metabolism and Endocrinology, Central South University, Changsha, China.
⁸ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. feixiong@tjh.tjmu.edu.cn.
⁹ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. szhang@tjh.tjmu.edu.cn.
¹⁰ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wangcy@tjh.tjmu.edu.cn.

^# Contributed equally.

PMID: 33462408
PMCID: PMC8185071
DOI: 10.1038/s41418-020-00714-7

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

Longmin Chen et al. Cell Death Differ. 2021 Jun.

. 2021 Jun;28(6):1880-1899.

doi: 10.1038/s41418-020-00714-7. Epub 2021 Jan 18.

Authors

Affiliations

¹ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Nephrology,Tongji Hospital, Tongji College of Medicine, Huazhong University of Science and Technology, Wuhan, China.
³ Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Tongji Hospital, Wuhan, China.
⁴ Clinical Molecular Immunology Center, Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China.
⁵ Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁶ ULB Center for Diabetes Research, Université Libre de Bruxelles, 808 Route de Lennik, B-1070, Brussels, Belgium.
⁷ Diabetes Center, The Second Xiangya Hospital, Institute of Metabolism and Endocrinology, Central South University, Changsha, China.
⁸ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. feixiong@tjh.tjmu.edu.cn.
⁹ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. szhang@tjh.tjmu.edu.cn.
¹⁰ The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wangcy@tjh.tjmu.edu.cn.

^# Contributed equally.

PMID: 33462408
PMCID: PMC8185071
DOI: 10.1038/s41418-020-00714-7

Abstract

Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2a^f/f, Kdm2a^-/-) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a^-/- increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a^-/- mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a^-/- macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a^-/- mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1. Obesity is featured by the reduced H3K36me2 levels in ATMs.**
H3K36me2 levels in epWAT (A) and scWAT (B) of mice fed ND or HFD for 8 weeks (n = 4/group). Flow cytometry analysis of H3K36me2 status in CD45⁺ cells from epWAT (C) and scWAT (D) of mice fed with ND or HFD for 8 weeks. Left: a representative flow cytometry data; right: quantitative data from all mice analyzed (n = 5/group). Representative FACS plots showing the proportion of F4/80⁺ cells gated on CD45⁺ cells from epWAT (E) and scWAT (F) of mice fed with ND or HFD for 8 weeks. Representative FACS plots and quantitative data of H3K36me2 levels in macrophages from epWAT (G) and scWAT (H) of mice after 8 weeks of HFD or ND feeding (n = 5/group). I Western blot analysis of H3K36me2 levels in CD45⁺ cells isolated from scWAT of controls (n = 4) and obese subjects (n = 4). J Representative immunostaining results for CD68 and H3K36me2 in scWAT sections from controls and obese subjects. Scale bars: 50 μm. Original magnification: ×400. Values are expressed as mean ± SEM, and unpaired Student’s t test was employed for data analysis. *P < 0.05; **P < 0.01.

**Fig. 2. *Kdm2a* deficiency orchestrates alternative activation of macrophages.**
A Strategy for generating a conditional *Kdm2a*-deficient model. *Kdm2a* exons 7–9 were flanked by a neo-flippase recognition target (FRT) and two loxP sites. The neo-gene was deleted after Flp recombination and the *Kdm2a* exons were then excised by Cre recombinase. B Western blot analysis of Kdm2a and H3K36me2 levels in BMDMs from WT and KO mice, and a bar graph showing data derived from three mice in each group. C Flow cytometry analysis of the expression of F4/80, CD11b, and CD11c in BMDMs stimulated with LPS for 24 h. The percentages of F4/80⁺CD11b⁺ and F4/80⁺CD11b⁺CD11c⁺ cells are shown. D RT-PCR analysis of relative mRNA expression of M1 marker genes in BMDMs stimulated with LPS for 6 h. E Flow cytometry analysis of the expression of F4/80, CD11b, and CD206 in BMDMs stimulated with IL-4 for 24 h. Percentages of F4/80⁺CD11b⁺CD206⁺ cells are shown in the bar graphic figure. F Western blot analysis of Arg1 expression in BMDMs stimulated with IL-4 with indicated time. G RT-PCR analysis of relative mRNA levels of M2 genes in BMDMs stimulated with IL-4 for 6 h. H Western blot analysis of Arg1 expression in peritoneal macrophages with or without IL-4 stimulation for 24 h. I RT-PCR analysis of relative mRNA levels of M2 genes in peritoneal macrophages stimulated with or without IL-4 for 6 h. J Representative FACS plots and the percentages of F4/80⁺CD11b⁺ cells in epWAT of ND-fed WT and KO mice at 16 weeks of age (n = 4/group). K Expression of CD206 in F4/80⁺CD11b⁺ cells as shown in (J). The amounts of F4/80⁺CD11b⁺CD206⁺ cells were quantified and shown as relative mean fluorescence intensity (MFI). Results are representative of three to four independent experiments (B–I). Values are expressed as mean ± SEM, and unpaired Student’s t test was used for data analysis. *P < 0.05; **P < 0.01; ***P < 0.001. ns not significant, ud undetected, Arg1 Arginase 1.

**Fig. 3. Loss of *Kdm2a* in myeloid cells upregulates Pparγ and promotes fatty acid uptake and oxidation.**
A A scatter plot representing the average gene expression levels (−log10) in KO relative to WT BMDMs upon IL-4 stimulation vs. fold changes (log2). Two biological replicates for WT mice and three for KO mice were included, and there were two mice for each biological replicate. B Heatmap showing the differentially expressed genes relevant to M2 program and genes related to lipid metabolism in IL-4-treated BMDMs. The data were generated from RNA deep sequencing as described. C RT-PCR analysis to confirm the relative mRNA abundance of *Pparg*, *Cd36*, *Lpl*, and *Plin3* in BMDMs treated with vehicle or IL-4 for 6 h. Representative western blot results for analysis of Pparγ, CD36, and Cpt1a expression in BMDMs before and after IL-4 stimulation (D), and bar graphs (E) showing the mean expression levels resulted from three independent replications. F Uptake of BODIPY-labeled C12-fatty acids in BMDMs treated with or without IL-4 by flow cytometry analysis, and a bar graphic figure showing the mean data derived from four independent replications. G Representative FACS plots and quantitative data showing the uptake of BODIPY-labeled C12-fatty acids in BMDMs under indicated conditions. H OCR of BMDMs derived from WT and KO mice following 24 h of IL-4 stimulation, which was assessed before and after sequential treatment with oligomycin, FCCP, rotenone, and antimycin A. I Basal OCR (left) and SRC (right) in cells shown in (H), and all data were presented as mean derived from four independent experiments. The values are presented as mean ± SEM. Significance was determined by unpaired Student’s t test in (C, E–G, I) (left panel) and by one-way ANOVA in (I) (right panel). *P < 0.05; **P < 0.01; ***P < 0.001. Cpt1a carnitine palmitoyltransferase 1a.

**Fig. 4. Loss of *Kdm2a* alleviates HFD-induced obesity and obesity-associated metabolic deterioration.**
A Representative images for WT and KO mice fed with HFD or ND for 16 weeks. B Body weight changes for WT and KO mice during the course of HFD or ND induction. Representative pictures and bar graphs of epWAT (C) and scWAT (D) mass collected from WT and KO mice after 16 weeks of HFD or ND feeding. Representative H&E staining and lipid droplet surface quantification of epWAT (E) and scWAT (F) from HFD- or ND-fed WT and KO mice. G Blood glucose levels between WT and KO mice under fasting condition. H Plasma insulin levels determined after 16 weeks of HFD or ND feeding. I Results of intraperitoneal glucose tolerance tests (left) and the areas under curves (AUC) for blood glucose levels (right). J Results for the intraperitoneal insulin tolerance tests and areas above curves (AAC). K Results for analysis of triglyceride (TG) levels in the plasma. L Results for TG levels in the liver. Representative H&E staining and Oil Red O staining of liver sections originated from ND (M) or HFD (N) fed WT and KO mice. ND, n = 4 per group; HFD, n = 11 for WT mice and n = 10 for KO mice. Scale bars: 100 μm (E, F); 50μm (M, N). Original magnification: ×200 (E, F); ×400 (M, N). Values are expressed as mean ± SEM and unpaired Student’s t test was employed for data analysis. *P < 0.05; **P < 0.01; ***P < 0.001.

**Fig. 5. *Kdm2a* deficiency alleviates macrophage accumulation and reverses the M1–M2 imbalance of ATMs in mice following HFD challenge.**
A Analysis of plasma cytokine levels between HFD-induced WT (n = 11) and KO (n = 10) mice. RT-PCR analyses of the mRNA abundance for the indicated genes in epWAT (B) and scWAT (C) (n = 6 per group). Representative images of immunostaining for F4/80 in epWAT (D) and scWAT (E) sections. The images were taken under ×400 magnification. Scale bar: 50 μm. Representative FACS plots, and the frequency and the number of ATMs in epWAT (F) and scWAT (G) in HFD-induced WT and KO mice. Representative FACS plots and quantitative data of M2 macrophages in epWAT (H) and scWAT (I) from HFD-induced WT and KO mice. Flow cytometry analysis of M1 macrophages in epWAT (J) and scWAT (K) from HFD-induced WT and KO mice. Left: a representative plot for flow cytometry; right: quantitative data resulted from all mice analyzed. n = 4 for each group (F–K). Values are presented as mean ± SEM, and unpaired Student’s t test was used for statistical analysis. *P < 0.05; **P < 0.01; ***P < 0.001.

**Fig. 6. Macrophages deficient in *Kdm2a* increase energy expenditure and adaptive thermogenesis.**
A Results for real-time recording of RER (left) and quantitative data (right) collected from four mice in each group for 24 h following 16 weeks of HFD induction (n = 4 per group). B Food intake (g) in WT and KO mice following 16 weeks of HFD induction measured in metabolic cages (n = 4 per group). RT-PCR results for analysis of thermogenic genes *Cox5a*, *Ucp1*, *Cox7a*, and *Cox8b* in BAT (C) and scWAT (D) from HFD challenged WT and KO mice (n = 6 for each group). E RT-PCR results for analysis of *Ucp1* in the epWAT following 16 weeks of HFD challenge (n = 6 for each group). F Daily rectal temperature of mice housed under 4 °C condition (n = 6 per group). G Analysis of the weight for BAT collected from WT and KO mice after cold exposure (n = 6 per group). H Representative western blot results (left) and bar graphs (right) showing the expression levels for BAT TH and Ucp1 (n = 4 per group). I Relative mRNA abundance of *Ucp1* in BAT of mice with (n = 6/group) or without cold stress (n = 3/group). Representative images of H&E staining (J) and Ucp1 IHC (K) of BAT sections with or without cold exposure (six images per mouse). Representative images of H&E staining (L) and Ucp1 IHC (M) of scWAT sections (six images per mouse). Scale bars: 50 μm (J–M). Original magnification: ×400 (J–M). Values are expressed as mean ± SEM, and unpaired Student’s t test was used for data analysis. *P < 0.05; **P < 0.01; ***P < 0.001. ns not significant.

**Fig. 7. Loss of *Kdm2a* promotes Pparγ transcription by inhibiting H3K36me2 demethylation along with chromatin remodeling.**
A Average ATAC-seq signal distribution near the TSS. B Average ATAC-seq signals spanning the entire genome visualized in a TSS-centric manner. C Volcano plot of the differentially accessible regions (DARs) between WT and KO BMDMs treated with IL-4 for 6 h, as determined by ATAC-seq. DARs with log2 (fold change) ≥ 0.5, and a P value ≤ 0.05 in KO BMDMs are shown in red (increased accessibility) or blue (decreased accessibility). D Scatter plot of the correlation between DEGs vs. DARs. The number of genes in the quadrants is shown as indicated. E ATAC-seq bedgraph panels of the *Pparg* locus showing the peak locations relative to the TSS. The panels were compared with ATAC signals between WT and KO BMDMs following IL-4 stimulation. F ATAC peak strength (y-axis) for the selected peaks within the *Pparg* locus. G Results of ChIP-qPCR to compare H3K36me2 levels in the DARs of *Pparg* in WT and KO BMDMs treated with vehicle or IL-4 for 6 h. H Results of ChIP-qPCR to compare H3K36me2 levels in the DARs of *Pparg* in si-Control or si-*Kdm2a* transfected RAW264.7 cells after IL-4 stimulation for 6 h. I Enrichment of TF binding motifs in DARs of KO BMDMs gained or lost vs. WT BMDMs after IL-4 treatment. J ChIP-qPCR was performed for Stat6 in the *Pparg* DARs in WT and KO BMDMs treated with IL-4. K Representative western blot results (above) and a dotted line graph (below) showing the temporal expression of p-Stat6 in BMDMs after IL-4 stimulation. The data in (A–F) and (I) were derived from two independent biological replicates, and there were two mice for each biological replicate. Data are representative of three independent experiments for figures (G, H, J, K). Values are presented as mean ± SEM. Statistical significance was determined by the unpaired Student’s t test in (B, F–H, J, K). *P < 0.05; **P < 0.01.

**Fig. 8. Kdm2a directly targets Pparγ to regulate alternative activation of macrophages.**
A OCR in WT and KO BMDMs stimulated with IL-4 for 24 h in the presence or absence of GW9662. B SRC in cells as shown in (A). C Western blot analysis of CD36 and Arg1 levels in WT and KO BMDMs under indicated culture conditions. D Flow cytometry analysis of the expression of F4/80, CD11b, and CD206 in BMDMs under indicated culture conditions. A bar graphic figure was employed to show the percentage of F4/80⁺CD11b⁺CD206⁺ cells in each group. Data were collected from four (A, B) or three independent experiments (C, D). Values are presented as mean ± SEM. Statistical significance was determined by the unpaired Student’s t test in (C), and by one-way ANOVA in (B, D). *P < 0.05; **P < 0.01; ***P < 0.001. ns not significant.

See this image and copyright information in PMC

Cited by

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization.
Chen L, Zhou Q, Fang X, Xu Q, Zou Y, Zhang J. Chen L, et al. Int J Nanomedicine. 2024 May 17;19:4411-4427. doi: 10.2147/IJN.S454445. eCollection 2024. Int J Nanomedicine. 2024. PMID: 38774028 Free PMC article.
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.
Taylor BC, Steinthal LH, Dias M, Yalamanchili HK, Ochsner SA, Zapata GE, Mehta NR, McKenna NJ, Young NL, Nuotio-Antar AM. Taylor BC, et al. Epigenetics Chromatin. 2024 Apr 27;17(1):12. doi: 10.1186/s13072-024-00536-8. Epigenetics Chromatin. 2024. PMID: 38678237 Free PMC article.
The molecular mechanism of macrophage-adipocyte crosstalk in maintaining energy homeostasis.
Zhang Y, Zhang B, Sun X. Zhang Y, et al. Front Immunol. 2024 Apr 8;15:1378202. doi: 10.3389/fimmu.2024.1378202. eCollection 2024. Front Immunol. 2024. PMID: 38650945 Free PMC article. Review.
Epigenetic modifications in obesity-associated diseases.
Long Y, Mao C, Liu S, Tao Y, Xiao D. Long Y, et al. MedComm (2020). 2024 Feb 24;5(2):e496. doi: 10.1002/mco2.496. eCollection 2024 Feb. MedComm (2020). 2024. PMID: 38405061 Free PMC article. Review.
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress.
Taylor BC, Steinthal LH, Dias M, Yalamanchili HK, Ochsner SA, Zapata GE, Mehta NR, McKenna NJ, Young NL, Nuotio-Antar AM. Taylor BC, et al. bioRxiv [Preprint]. 2024 Jan 22:2023.07.30.551059. doi: 10.1101/2023.07.30.551059. bioRxiv. 2024. Update in: Epigenetics Chromatin. 2024 Apr 27;17(1):12. doi: 10.1186/s13072-024-00536-8. PMID: 38328142 Free PMC article. Updated. Preprint.

See all "Cited by" articles

References

1. Cheng J, Song J, He X, Zhang M, Hu S, Zhang S, et al. Loss of Mbd2 protects mice against high-fat diet-induced obesity and insulin resistance by regulating the homeostasis of energy storage and expenditure. Diabetes. 2016;65:3384–95. doi: 10.2337/db16-0151. - DOI - PubMed
1. van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL. Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics. 2015;7:66. doi: 10.1186/s13148-015-0101-5. - DOI - PMC - PubMed
1. Li Q, Zou J, Wang M, Ding X, Chepelev I, Zhou X, et al. Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nat Commun. 2014;5:5780. doi: 10.1038/ncomms6780. - DOI - PMC - PubMed
1. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811–6. doi: 10.1038/nature04433. - DOI - PubMed
1. Zhu L, Li Q, Wong SH, Huang M, Klein BJ, Shen J, et al. ASH1L links histone H3 lysine 36 dimethylation to MLL leukemia. Cancer Discov. 2016;6:770–83. doi: 10.1158/2159-8290.CD-16-0058. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations
- scite Smart Citations
Medical
- Genetic Alliance
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

[1] Cheng J, Song J, He X, Zhang M, Hu S, Zhang S, et al. Loss of Mbd2 protects mice against high-fat diet-induced obesity and insulin resistance by regulating the homeostasis of energy storage and expenditure. Diabetes. 2016;65:3384–95. doi: 10.2337/db16-0151. - DOI - PubMed

[2] Cheng J, Song J, He X, Zhang M, Hu S, Zhang S, et al. Loss of Mbd2 protects mice against high-fat diet-induced obesity and insulin resistance by regulating the homeostasis of energy storage and expenditure. Diabetes. 2016;65:3384–95. doi: 10.2337/db16-0151. - DOI - PubMed

[3] van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL. Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics. 2015;7:66. doi: 10.1186/s13148-015-0101-5. - DOI - PMC - PubMed

[4] van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL. Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics. 2015;7:66. doi: 10.1186/s13148-015-0101-5. - DOI - PMC - PubMed

[5] Li Q, Zou J, Wang M, Ding X, Chepelev I, Zhou X, et al. Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nat Commun. 2014;5:5780. doi: 10.1038/ncomms6780. - DOI - PMC - PubMed

[6] Li Q, Zou J, Wang M, Ding X, Chepelev I, Zhou X, et al. Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nat Commun. 2014;5:5780. doi: 10.1038/ncomms6780. - DOI - PMC - PubMed

[7] Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811–6. doi: 10.1038/nature04433. - DOI - PubMed

[8] Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811–6. doi: 10.1038/nature04433. - DOI - PubMed

[9] Zhu L, Li Q, Wong SH, Huang M, Klein BJ, Shen J, et al. ASH1L links histone H3 lysine 36 dimethylation to MLL leukemia. Cancer Discov. 2016;6:770–83. doi: 10.1158/2159-8290.CD-16-0058. - DOI - PMC - PubMed

[10] Zhu L, Li Q, Wong SH, Huang M, Klein BJ, Shen J, et al. ASH1L links histone H3 lysine 36 dimethylation to MLL leukemia. Cancer Discov. 2016;6:770–83. doi: 10.1158/2159-8290.CD-16-0058. - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

Affiliations

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous