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《分子遗传学专题》之九

时间:周五(1123日)13:30  地点:一教

题目:植物表观遗传调控机理研究

授课人简介:曹晓风,博士,研究员,博士生导师

学习经历:(从大学开始)
1984-1988
  北京大学生物系
学士
1988-1991
  中国农业大学生物学院
硕士
1993-1997
  北京大学生命科学学院 
博士


工作经历

1991-1993
  北京大学生命科学学院
助教
1993-1997
  北京大学生命科学学院
讲师
1995-1996
  英国John Innes Centre
访问学者
1997-1998
  美国华盛顿州立大学生化研究所
博士后
1999-2003
  美国加州大学洛杉矶分校
助理研究员
2003-今
  中科院遗传与发育生物学研究所
研究员


获奖情况
2008年获得美国杜邦青年科学家奖
2006年“百人计划”终期评估中获得优秀
2003年获国家杰出青年基金
2002年入选中科院“百人计划”

主要研究领域
        表观遗传学(Epigenetics) 指的是研究基因功能的变化,这种变化在有丝分裂和/或减数分裂中是可以遗传的,与一般遗传学不同的是,所研究的基因不存在DNA序列上的改变。从广义上讲,表观遗传学控制基因功能主要包括以下三个方面:基因本身的DNA甲基化;基因所在的核小体上的组蛋白的共价修饰、染色质核小体的重塑和核小体变种以及近年来发现的小分子RNA介导的转录和转录后水平的基因沉默。随着表观遗传调控机理研究的深入和相关研究技术的突破,在基因组水平上研究各种植物、不同发育阶段和各种生长条件的表观遗传图谱的表观遗传组学正在蓬勃兴起,为揭示高等植物生长发育的分子机理提供了新手段和新思路。本实验室运用拟南芥和水稻为材料,研究组蛋白修饰以及小的非编码RNA如何影响基因表达以及植物发育,主要研究方向为组蛋白甲基化对拟南芥开花时间的调控和水稻小RNA合成调控及其对植物发育的机理研究。

 
 
 
      

拟南芥中的组蛋白甲基化与开花时间调控的分子机理研究
        在真核生物的细胞核中,许多细胞生理活动都以染色体为模板来进行。作为染色体的组分之一,组蛋白延伸出来的 N末端可以发生多种翻译后修饰,这些修饰的不同组合构成了在DNA序列之外的另一个层面上的遗传信息并发挥着重要功能。在动物中,人们鉴定了一些催化组蛋白甲基化与去甲基化过程的酶,编码这些酶的基因分属于几个重要的基因家族。组蛋白甲基化是组蛋白修饰当中最为重要也是最为复杂的一种修饰。对组蛋白H3、H4上赖氨酸残基甲基化的进一步研究证明,组蛋白甲基化在维持染色体功能以及各种细胞生理活动的调控过程中发挥着重要作用,其中包括对染色体结构和基因表达的调节、异染色质的形成、基因印记、基因组稳定性和其他重要的细胞生理活动。另外,精氨酸的甲基化和去甲基化的重要作用也逐渐被证明,研究表明,精氨酸甲基化参与了转录调控、RNA加工、核运输、DNA损伤的响应以及信号转导等过程。最近,人们发现了一大类赖氨酸和精氨酸去甲基化酶,这些酶都含有一个保守的JmjC结构域。甲基化的动态平衡是通过对甲基化和去甲基化这两个过程的控制来实现的。在拟南芥的基因组中存在着许多含有SET结构域的蛋白、蛋白质精氨酸甲基转移酶以及含有JmjC结构域的蛋白。我们通过生物化学和反向遗传学的手段鉴定出了一些新的组蛋白甲基转移酶和去甲基化酶,并试图借此来理解组蛋白甲基化在植物发育过程中所发挥的重要作用。
        开花时间对于植物是非常重要的,植物通过响应外源环境和内源的信号,在合适的时间开花,才能尽可能成功地繁殖后代。目前的研究已经证实,植物开花时间受光周期通路、赤霉素(GA)通路、春化通路和自主通路的调控。已有研究表明,包括乙酰化、赖氨酸甲基化和泛素化在内的组蛋白修饰在植物开花时间的调控中发挥着重要作用。在拟南芥中,蛋白质精氨酸甲基化作为一种翻译后修饰,也参与了植物开花时间的调控。我们之前的工作已经证实在拟南芥中,AtPRMT5(protein arginine methyltransferase)、AtPRMT10、AtPRMT4a/4b以及AtHAC1(histone acetyltransferase)通过抑制FLC的表达促进开花。本实验室研究的主要方向之一是研究组蛋白修饰的重要因子在调控拟南芥开花时间中的分子机理。 

WT

atprmt4a

atprmt4b

atprmt4a atprmt4b

 

高等植物中small RNA的合成途径调控机理研究
        RNA沉默在植物发育过程中的作用是近期研究关注的焦点。miRNAsiRNA是两类具有调节功能的RNA小分子,在发育调控、基因组稳定性和病毒防御方面发挥重要作用。miRNAsiRNA很相似,但其起源、形成过程不同。DICER或者DICER-LIKE (DCL)miRNAsiRNA生物合成途径中发挥关键作用,小分子RNA成熟后会整合到不同的RISC 复合体 (RNA-Induced Silencing Complexes)中发挥作用。 
        水稻(Oryza sativa L.)作为世界上最重要的农作物之一,是进行单子叶植物基因组学和分子生物学研究的模式物种。水稻中存在多个DCL蛋白,其功能在单双子叶植物分化之前就已经分化。本研究组以水稻为模式生物,重点研究水稻小分子RNA的合成途径,期望阐释small RNA在水稻发育过程中的调控网络。

        本研究组从水稻中鉴定了一批新的miRNA,如OsmiR528, OsmiR529OsmiR530等;获得了OsDCL1IR OsDCL4IR两个功能缺失突变体,证明OsDCL1 OsDCL4 在水稻发育过程中发挥重要作用。进一步研究发现, OsDCL1miRNA的累积起主要作用;OsDCL4主要负责对21nt siRNA进行加工。本研究组的长期研究目标之一是以水稻为模式生物,深入研究small RNA合成途径的分子机理和小分子RNA在水稻发育过程中的重要作用。 

代表性论文:

1.LifangNiu, Falong Lu, Taolan Zhao, Chunyan Liu and Xiaofeng Cao* (2012)The enzymatic activity of Arabidopsis proteinarginine methyltransferase 10 is essential forflowering time regulation. Protein & Cell. 3(6): 450-459. (Cover story)

2.Ahmad and Xiaofeng Cao* (2012)PlantPRMTsBroaden the Scope of ArginineMethylation.Journal of Genetics and Genomics. 39(5): 195-236.

3.Changhui Sun, Jun Fang, Taolan Zhao, Bo Xu, Fantao Zhang, Linchuan Liu, Jiuyou Tang, Genfa Zhang, Xiaojian Deng, Fan Chen, QianQian, Xiaofeng Cao and Chengcai Chu (2012) The histone methyltransferase SDG724 mediates H3K36me2/3 deposition at MADS50 and RFT1, and promotes flowering in rice. The Plant Cell. doi/10.1105/tpc.112.101436.

4.Xianwei Song, Dekai Wang, Lijia Ma, Zhiyu Chen, Pingchuan Li, Xia Cui, Chunyan Liu, Shouyun Cao, Chengcai Chu, Yuezhi Tao and Xiaofeng Cao* (2012) Rice RNA-dependent RNA polymerase 6 acts in small RNA biogenesis and spikelet development. The Plant Journal, 71:378-389.

5.Xianwei Song,Pingchuan Li,JixianZhai, Ming Zhou,Lijia Ma, Bin Liu, Dong-HoonJeong,Mayumi Nakano, Shouyun Cao, Chunyan Liu, Chengcai Chu, Xiu-Jie Wang, Pamela J. Green, Blake C. Meyers and Xiaofeng Cao* (2012) Roles of DCL4 and DCL3b in rice phased small RNA biogenesis. The Plant Journal, 69:462-474.

6.Falong Lu, Xia Cui,Shuaibin Zhang, Thomas Jenuwein, Xiaofeng Cao*(2011)Arabidopsis REF6 is a Histone H3 Lysine 27 Demethylase. Nature Genetics, 43:715-719.

7.Yuan Cheng, Monica Frazier, Falong Lu, Xiaofeng Cao, Matthew R. Redinbo(2011)Crystal Structure of the Plant Epigenetic Protein Arginine Methyltransferase 10. Journal of Molecular Biology,  414(1): 106-122.

8.Xigang Liu, Yun Ju Kim, Ralf Müller, Rae Eden Yumul, Chunyan Liu, Yanyun Pan, Xiaofeng Cao, Justin Goodrich, and Xuemei Chen (2011) AGAMOUS terminates floral stem cells by directly repressing the stem cell maintenance gene WUSCHEL through the recruitment of Polycomb Group proteins in Arabidopsis. The Plant Cell, 23(10): 3654-3670.

9.Ayaz Ahmad, Yuzhu Dong and Xiaofeng Cao*(2011) Characterization of the PRMT gene family in rice reveals conservation of arginine methylation. PLoS One, 6(8): e22664.

10.Xiaofeng Cao(2011) Special issue on epigenetic inheritance by histone modifications, histone variants and non-coding RNAs. Frontier in Biology,6: 87-87. (Editorial)

11.LijuanJi, Xigang Liu, Jun Yan, Wenming Wang, Rae Eden Yumul, Yun Ju Kim, Thanh Theresa Dinh, Jun Liu, Xia Cui, BinglianZheng, Manu Agarwal, Chunyan Liu, Xiaofeng Cao, Guiliang Tang, Xuemei Chen(2011)ARGONAUTE10 and ARGONAUTE1regulate the termination of floral stem cells through two microRNAs in Arabidopsis.PLoS Genetics, 7(3): e1001358.

12.Xian Deng, LianfengGu,Chunyan Liu, Tiancong Lu, Falong Lu, Zhike Lu, Peng Cui, Yanxi Pei, Baichen Wang, Songnian Hu, and Xiaofeng Cao* (2010) Arginine methylation mediated by AtPRMT5 is essential for proper pre-mRNA splicing. Proc. Natl. Acad. Sci. USA,107:19114-19119.

13.Chunyan Liu, Falong Lu, Xia Cui and Xiaofeng Cao*(2010) Histone methylation in higher plants. Annu Rev. Plant Biol. 61: 395-425.

14.Soichi Inagaki, Asuka Miura-Kamio, Yasukazu Nakamura, Falong Lu, Xia Cui, Xiaofeng Cao*, Hiroshi Kimura, Hidetoshi Saze, and TetsujiKakutani*(2010) Autocatalytic mechanisms for differential epigenetic modifications between genes and transposons within the Arabidopsis genome.EMBO Journal,29: 3496 – 3506 (* corresponding author).

15.Falong Lu, Xia Cui, Shuaibin Zhang, Chunyan Liu and Xiaofeng Cao* (2010) JMJ14 is an H3K4 demethylase and regulates flowering time in Arabidopsis. Cell Res. 20:387-390.

16.Ming Zhou, LianfengGu, Pingchuan Li, Xianwei Song, Liya Wei, Zhiyu Chen, and Xiaofeng Cao* (2010) Degradome sequencing reveals endogenous small RNA targets in rice (Oryza sativa L. ssp. indica). Frontier in Biology. 5(1): 67–90.

17.Ayaz Ahmad, Yong Zhang and Xiaofeng Cao*(2010) Decoding the epigenetic language of plant development. Molecular Plant. 3(4):719-728.

18.Ian R. Henderson, Simon R. Chan, Xiaofeng Cao, Lianna Johnson and Steven E. Jacobsen(2010) Accurate sodium bisulfite sequencing in plants. Epigenetics, 5, 29-31.

19.Xinyu Jian, Lin Zhang, Guanglin Li, Liang Zhang, Xiujie Wang, Xiaofeng Cao, Xiaohua Fang, Fan Chen (2010) Identification of novel stress-regulated microRNAs from Oryza sativa L.Genomics. 47-55.

20.Yanwei Wang, Pingchuan Li, Xiaofeng Cao, Xiujie Wang, Aimin Zhang and Xia Li (2009) Identification and expression analysis of miRNAs from nitrogen-fixing soybean nodules. Biochemical and Biophysical Research Communications, 378 (4): 799-803.

21.Blake C. Meyers, Michael J. Axtel, Bonnie Bartel, David P. Bartel, David Baulcombe, John L. Bowman, Xiaofeng Cao, James C. Carrington, Xuemei Chen,  Pamela J. Green, Sam Griffiths-Jones, Steven E. Jacobsen, Allison C. Mallory, Robert A. Martienssen, R. Scott Poethig, Yijun Qi, HerveVaucheret, Franck Vazquez, Olivier Voinnet, DetlefWeigel and Jian-Kang Zhu (2008) CRITERIA FOR ANNOTATION OF PLANT microRNAs. The Plant Cell, 20, 3186-3190.

22.Séverine Lacombe, Hiroshi Nagasaki,Carole Santi1,David Duval,Beno?tPiégu, Martine Bangratz, Jean-Christophe Breitler, Emmanuel Guiderdoni, Christophe Brugidou, Xiaofeng Cao, Claire Brice, Olivier Panaud, WojciechKarlowski, Yutaka Sato and Manuel Echeverria (2008) Identification of precursor transcripts for 6 novel miRNAs expands the diversity on the genomic organisation and expression of miRNA genes in rice.  BMC Plant Biology. 8: 123.

23.LifangNiu, Yong Zhang, Yanxi Pei, Chunyan Liu and Xiaofeng Cao*(2008)Redundant Requirement for a Pair of Protein Arginine Methyltransferase 4 Homologs for the Proper Regulation of Arabidopsis Flowering Time. Plant Physiology 148:490-503.

24.Dongfen Zhang, Qiuying Yang, Yong Ding, Xiaofeng Cao, YongbiaoXue, Zhukuan Cheng (2008) Cytological characterization of the tandem repetitive sequences and theirmethylation status in the Antirrhinum majus genome. Genomics92: 107–114

25.Falong Lu, Guanglin Li, Xia Cui, Chunyan Liu, Xiu-Jie Wang and XiaofengCao*(2008) Comparative Analysis of JmjC Domain-containing Proteins Reveals the Potential Histone Demethylases in Arabidopsis and Rice.Journal of Integrative Plant Biolog. 50 (7): 886–896.

26.JixianZhai, Jun Liu, Bin Liu, Pingchuan Li, Blake C. Meyers, Xuemei Chen and Xiaofeng Cao* (2008) Small RNA-directed Epigenetic Natural Variation in Arabidopsis thaliana. PLoS Genetics4(4): e1000056.
Comments: http://www.nature.com/nchina/2008/080514/full/nchina.2008.110.html

27.Cheng Lu, Dong-Hoon Jeong, Karthik Kulkarni, Manoj Pillay, Kan Nobuta,  Rana German, Shawn R. Thatcher,  Christopher Maher, Lifang Zhang, Doreen Ware, Bin Liu, Xiaofeng Cao, Blake C. Meyers andPamela J. Green (2008)Genome-wide analysis for discovery of new rice miRNAs reveals natural antisense miRNAs (nat-miRNAs).Proc. Natl. Acad. Sci., USA105, 4951-4956.

28.Lifang Niu, Falong Lu, Yanxi Pei, Chunyan Liu and Xiaofeng Cao*(2007)Regulation of Flowering Time by a Protein Arginine Methyltransferase, AtPRMT10. EMBO Reports8(12):1190-1195.

29.Bin Liu, Zhiyu Chen, Xianwei Song, Chunyan Liu, Xia Cui, Xianfeng Zhao, Jun Fang, WenyingXu, Huiyong Zhang, Xiujie Wang, Chengcai Chu, Xingwang Deng, YongbiaoXue and Xiaofeng Cao* (2007) Oryza sativa DICER-LIKE 4 Reveals a Key Role for siRNA Silencing in Plant Development. The Plant Cell19:2705-2718.
Comments: http://www.nature.com/nchina/2007/071024/full/nchina.2007.224.html

30.Dongsheng Yan, Yong Zhang, LifangNiu, Yi Yuan and Xiaofeng Cao*(2007) Identification and characterization of two closely related histone H4 arginine 3 methyltransferases in Arabidopsis thaliana. Biochem J408:113-121.

31.Yanxi Pei, LifangNiu, Falong Lu, Chunyan Liu, JixianZhai, Xiangfeng Kong and Xiaofeng Cao*(2007). Mutations in the Type II protein arginine methyltransferase AtPRMT5 result in pleiotropic developmental defects in Arabidopsis thaliana. Plant Physiology 144:1913-1923.

32.Weiwei Deng, Chunyan Liu, Yanxi Pei, Xian Deng, LifangNiu and Xiaofeng Cao*(2007) Involvement of the Histone Acetyltransferase AtHAC1 in the Regulation of Flowering Time via Repression of FLC in Arabidopsis thaliana. Plant Physiology 143:1660-1668.

33.Yong Ding, Xia Wang, Lei Su, JixianZhai, Shouyun Cao, Dongfen Zhang, Chunyan Liu, Yuping Bi, QianQian, Zhukuan Cheng, Chengcai Chu, and Xiaofeng Cao* (2007) SDG714, a histone H3K9 methyltransferase involves in Tos17 DNA methylation and transposition in Oryza sativa L.The Plant Cell19:9-22.
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34.Ran Xia, Junguo Wang, Chunyan Liu, Yu Wang,Youqun Wang, JixianZhai, Jun Liu, Xuhui Hong, Xiaofeng Cao, Jian-Kang Zhu, Zhizhong Gong(2006)ROR1/RPA2A encoding a putative replication protein A2 is required for maintaining epigenetic gene silencing and important for root and shoot meristem development in Arabidopsis. ThePlant Cell18: 85–103.

35.Bin Liu, Pingchuan L , Xin Li, Chunyan Liu, Yunru Cao, Chengcai Chu, Xiaofeng Cao* (2005). Loss of Function of OsDCL1 Affects MicroRNA Accumulation and Causes Developmental Defects in Rice. Plant Physiology139: 296–305.

36.Wenli Zhang, Chuandeng Yi, WeidongBao, Bin Liu, Jiajun Cui, Hengxiu Yu, Xiaofeng Cao, MinghongGu, Min Liu, Zhukuan Cheng (2005). The Transcribed 165-bp CentO Satellite Is the Major Functional Centromeric Element in the Wild Rice Species Oryza punctata. Plant Physiology139:306–315.

37.Hong Li, Lin Xu, Hua Wang, Zheng Yuan, Xiaofeng Cao, Zhongnan Yang, Dabing Zhang, YuquanXu,Hai Huang (2005). The Putative RNA-Dependent RNA Polymerase RDR6 Acts Synergistically withASYMMETRIC LEAVES1 and 2 to Repress BREVIPEDICELLUS and MicroRNA165/166 in Arabidopsis Leaf Development.The Plant Cell17:2157–2171.

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