组蛋白H3的22个赖氨酸去甲基化酶对胎鼠棕色脂肪细胞分化的调控作用

武晓慧; 徐玉乔; 张丰; 郜松; 魏佳昶; 许久航; 李青; 苏兴利

您当前的位置：

首页 >

文章列表页 >

组蛋白H3的22个赖氨酸去甲基化酶对胎鼠棕色脂肪细胞分化的调控作用

基础研究 | 更新时间：2023-11-01

- 组蛋白H3的22个赖氨酸去甲基化酶对胎鼠棕色脂肪细胞分化的调控作用
- Regulation of 22 Lysine Demethylases of Histone H3 on the Differentiation of BrownAdipocytes in Fetal Mice
- 中山大学学报（医学科学版） 2020年41卷第4期页码：534-541
- 作者机构：
  
  1.西安医学院肥胖与代谢病研究所，陕西西安 710021
  2.空军军医大学第一附属医院病理科暨病理学教研室，陕西西安 710032
  3.空军军医大学学员队，陕西西安 710032
  4.西安医学院教务处，陕西西安 710021
- 作者简介：
  
  武晓慧，博士，副教授，研究方向：表观遗传与代谢性疾病，E-mail:wuxh5221170@126.com
- 基金信息：
  
  国家自然科学基金(81572631;31000559);西安医学院配套基金(2018PT37);西安医学院高层次人才科研基金(2018RCYJ01)
- DOI：
  中图分类号： R364.2
- 纸质出版日期：2020-07-15，
  
  收稿日期：2020-01-12，
扫描看全文
武晓慧,徐玉乔,张丰等.组蛋白H3的22个赖氨酸去甲基化酶对胎鼠棕色脂肪细胞分化的调控作用[J].中山大学学报（医学科学版）,2020,41(04):534-541.

WU Xiao-hui,XU Yu-qiao,ZHANG Feng,et al.Regulation of 22 Lysine Demethylases of Histone H3 on the Differentiation of BrownAdipocytes in Fetal Mice[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):534-541.
武晓慧,徐玉乔,张丰等.组蛋白H3的22个赖氨酸去甲基化酶对胎鼠棕色脂肪细胞分化的调控作用[J].中山大学学报（医学科学版）,2020,41(04):534-541. DOI：

WU Xiao-hui,XU Yu-qiao,ZHANG Feng,et al.Regulation of 22 Lysine Demethylases of Histone H3 on the Differentiation of BrownAdipocytes in Fetal Mice[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):534-541. DOI：

摘要

目的

探索胎鼠棕色脂肪细胞分化过程中组蛋白H3赖氨酸残基位点H3k4，H3k9，H3k27，H3k36的22种去甲基化酶的调控作用，为棕色脂肪细胞分化研究提供理论基础。

方法

收集怀孕时间为E13.5~E19.5 d的小鼠胚胎，每个时间点至少取3只胎鼠。取肩胛间区棕色脂肪，进行HE染色，镜下观察棕色脂肪细胞的分化情况。Realtime RT-qPCR法检测随着小鼠胚胎的发育成熟，棕色脂肪标志基因

Ucp1

、

Cidea

、

Prdml6

及脂肪细胞分化基因

Pparγ

的表达情况和棕色脂肪中组蛋白H3的22种赖氨酸去甲基化酶的基因表达情况。Westen blot法检测棕色脂肪组织中Ucp1的蛋白表达。

结果

最早在E14.5 d的胎鼠背部肩胛间区观察到棕色脂肪组织；E18.5 d胎鼠棕色脂肪细胞中出现光镜下可见的脂滴。与E15.5 d相比，

Ucp1

、

Cidea

、

Prdm16

及

Pparγ

的表达升高（

0.05）；Ucp1的蛋白表达增加（

0.05）。与E15.5 d相比，H3k4的去甲基化酶中，

Jarid1a

、

Jarid1b

、

Jarid1d

、

Lsd1

基因表达减少（

＜0.05），

Jarid1c

表达差异无统计学意义（

＞0.05）。在H3k9的去甲基化酶中，

Jmjd2a

、

Jmjd2b

、

Jmjd2c

、

Phf2

、

Jmjd1c

、

Jhdm2a

基因表达减少（

＜0.05）；

Phf8

、

Jhdm2b

、

Jmjd2d

基因表达增加（

＜0.05），

MINA

表达差异无统计学意义（

＞0.05）。在H3k36的去甲基化酶中，

Jmjd4

、

Jmjd5

、

Jhdm1b

表达减少（

＜0.05），

Jhdm1a

表达增加（

＜0.05）。在H3k27的去甲基化酶中，

Jmjd3

、

Utx

、

Jhdm1d

表达增加（

＜0.05）。

结论

在小鼠胚胎期棕色脂肪细胞的分化过程中，H3k4和H3k36去甲基化酶主要表现为基因表达下调，H3k9和H3k27去甲基化酶部分基因表达上调，这些去甲基化酶构成以转录激活和转录延长为主要效应的复杂调控网络。

Abstract

Objective

To explore the effects of 22 demethylases of histone H3k4

H3k9

H3k27 and H3k36 on the differentiation of fetal mice brown adipocytes

so as to provide a theoretical basis for the study of differentiation of brown adipocytes.

Methods

We collected the embryos from pregnant mice at stages E13.5 to E19.5

with no less than 3 fetal mice obtained at each time point. Then we isolated interscapular brown adipose tissues (BAT) for HE staining and observed the differentiation of brown adipocytes under a microscope. Realtime RT-qPCR was used to test the expression of BAT markers such as

Ucp1

Cidea

and

Prdm16

adipocyte differentiation related gene

Pparγ

and 22 lysine demethylases of histone H3 in BAT. Ucp1 protein expression in BAT was detected by Western blot.

Results

BAT were first observed in the interscapular area of fetal mice at E14.5. Lipid droplets were observed under light microscope in the brown adipocytes of fetal mice at E18.5. Compared with those in E15.5 embryos

in E16.5 to E19.5 embryos

the expression of

Ucp1

Cidea

Prdm16

and

Pparγ

increased (

0.05) and Ucp1 protein expression increased (

0.05). Of H3k4 demethylases

Jarid1a

Jarid1b

Jarid1d

and

Lsd1

showed decrease in expression (

0.05);

Jarid1c

expression had no statistical significance (

0.05). Of H3k9 demethylases

Jmjd2a

Jmjd2b

Jmjd2c

Phf2

Jmjd1c and

Jhdm2a

showed decrease in expression (

0.05);

Phf8

Jhdm2b

and

Jmjd2d

showed increase in expression (

0.05);

MINA

expression had no statistical difference (

0.05). Of H3k36 demethylases

Jmjd4

Jmjd5

and

Jhdm1b

showed

decrease in expression (

0.05);

Jhdm1a

showed increase in expression (

0.05). Of H3k27 demethylases

Jmjd3

Utx

and

Jhdm1d

showed increase in expression (

0.05).

Conclusion

In the process of brown adipocytes differentiation

expressions of H3k4 and H3k36 demethylases were mainly downregulated and those of some H3k9 and H3k27 demethylases were upregulated. These demethylases formed a complex regulatory network with transcriptional activation and transcriptional elongation as the main effects.

关键词

棕色脂肪细胞分化组蛋白H3去甲基化酶

Keywords

brown adipocytesdifferentiationhistone H3demethylase

references

Lee SY, Chang HJ, Sung J, et al. The impact of obesity on subclinical coronary atherosclerosis according to the risk of cardiovascular disease[J]. Obesity, 2014, 22(7): 1762-1768.

Sidossis L, Kajimura S. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis[J]. J Clin Invest, 2015, 125(2): 478-486.

Rodrigo FV, Kara LM, Eric RR, et al. Contribution of brown adipose tissue to human energy metabolism[J]. Mol Aspects Med, 2019, 68: 82-89.

涂清强. 温度对乳腺癌小鼠棕色脂肪18F-FDG Micro-PET/CT成像的影响[J]. 中山大学学报（医学科学版），2020, 41（4）：558-562.

TU Qing-qiang. Effects of temperature on 18F-FDG Micro-PET/CT imaging of brown adipose tissue in tumor mice [J]. J SUN Yat-sen Univ (Med Sci), 2020, 41(4)：558-562.

Lee P, Bova R, Schofield L, et al. Brown adipose tissue exhibits a glucose-responsive thermogenic biorhythm in humans[J]. Cell Metab, 2016, 23(4): 602-609.

Lee P, Ho KK, Fulham MJ. The importance of brown adipose tissue[J]. N Engl J Med, 2009, 361(4):418-420.

Pan D, Huang L, Zhu LJ, et al. Jmjd3-mediated H3K27me3 dynamics orchestrate brown fat development and regulate white fat plasticity[J]. Dev Cell, 2015, 35(5): 568-583.

Zha L, Li F, Wu R, et al. The histone demethylase utx promotes brown adipocyte thermogenic program via coordinated regulation of H3K27 demethylation and acetylation[J]. J Biol Chem, 2015, 290(41): 25251-25163.

Birsoy K, Berry R, Wang T, et al. Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis[J]. Development, 2011, 138(21): 4709-4719.

Matsumura Y, Nakaki R, Inagaki T, et al. H3K4/H3K9me3 bivalent chromatin domains targeted by lineage-specific DNA methylation pauses adipocyte differentiation[J]. Mol Cell, 2015, 60(4): 584-596.

Lee KH, Ju UI, Song JY, et al. The histone demethylase PHF2 promotes fat cell differentiation as an epigenetic activator of both C/EBPα and C/EBPδ[J]. Mol Cells, 2014, 37(10): 734-741.

Duteil D, Tosic M, Lausecker F, et al. Lsd1 Ablation triggers metabolic reprogramming of brown adipose tissue[J]. Cell Rep, 2016, 17(4): 1008-1021.

Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch[J]. Nature, 2008, 454(7207): 961-967.

Rosen ED, Spiegelman BM. What we talk about when we talk about fat[J]. Cell, 2014, 156(1-2): 20-44.

Satoshi I, Wei Ch, Tomoyoshi N, et al. PRDM16 enhances nuclear receptor-dependent transcription of the brown fat- specific Ucp1 gene through interactions with mediator subunit MED1[J]. Genes Dev, 2015, 29(3): 308-321.

Gonzalez HE, Lee J, Choi J, et al. Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing[J]. Mol Metab, 2018, 7: 45-56.

Swigut T, Wysocka J. H3K27 demethylases, at long last[J]. Cell, 2007, 131(1): 29-32.

Tachibana M, Nozaki M, Takeda N, et al. Functional dynamics of H3K9 methylation during meiotic prophase progression[J]. EMBO J, 2007, 26(14): 3346-3359.

Labbé RM, Holowatyj A, Yang ZQ. Histone lysine demethylase (KDM) subfamily 4: structures, functions and therapeutic potential[J]. Am J Transl Res, 2014, 6(1): 1-15.

Dou Y, Milne TA, Ruthenburg AJ, et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components[J]. Nat Struct Mol Biol, 2006, 13(8): 713-719.

Hsia DA, Tepper CG, Pochampalli MR, et al. KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation[J]. Proc Natl Acad Sci USA, 2010, 107(21): 9671-9676.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

DANCR在人胚胎干细胞向内胚层分化中的调控功能

冷冻保存时长对卵裂期胚胎组蛋白表观遗传修饰的影响

INI1 诱导上皮样肉瘤细胞向脂肪方向分化

1-磷酸神经鞘氨醇对大鼠骨骼肌成肌细胞分化的影响