Epigenomes in plants, animals and fungi


Pao-Yang Chen's Laboratory


Next generation genetics

Next-generation or massively parallel DNA sequencing technologies have the potential to markedly accelerate genetics research. In our lab we perform DNA-seq for whole genome assembly, mRNA-seq for transcriptome studies, ChIP-seq for protein-DNA binding and histone marks, ATAC-seq for chromatin accessibility, and BS-seq for DNA methylation profiling (WGBS and RRBS). Our goal is to integrate both experiments and statistical methods and bioinformatic software to address biologically relevant questions.

次世代DNA定序技術對於現代基因學研究有重大的影響。我們實驗室利用DNA-seq重現全基因體序列,了解各個物種的基因特徵、RNA-seq的轉錄組學研究上,分析基因表達程度、ChIP-seq 分析蛋白質與DNA的的交互作用位點、ATAC-seq可揭露染色質上的開放位置、Bisulfite seuqencing (WGBS and RRBS)利用次世代定序建立全基因組的DNA甲基化圖譜,用以研究表觀基因的調控機制。我們針對次世代DNA定序設計並建立最新的樣品資料 (library) 進行實驗,同時針對產生的龐大資料,研究統計方法,並發展計算工具,以解讀生物學上相關的問題。


動物和植物的基因組DNA甲基化的遺傳標記隱藏著很重要的生物學意義。我們的實驗室與國內外多個實驗室有合作計畫,共同研究各樣植物和動物的DNA甲基化模式。例如,我們希望對基因改良的水稻基因體及表觀基因體進行詳細的研究分析。這個結果將增進水稻基因改良的品質以及轉殖的效率。還有,我們將藉由收集老鼠胎兒檢體,研究試管嬰兒的全基因體DNA甲基化 (methylome)的分布,來釐清試管胚胎植入對胚胎的表關遺傳圖譜的影響力。新的定序技術讓我們可以分析全基因體的DNA甲基化模式,初步的結果令人振奮。近期我們在人類生殖細胞的表觀基因體研究,發表了人類第一個表觀基因體重置的圖譜,是近期研究上的重大突破,我們並展開一連串的相關研究,探討此一遺傳上獨特且重要的細胞。


Lab Members

2018-NOW Associate Research Fellow, IPMB, Academia Sinica
2012-2018 Assistant Research Fellow, IPMB, Academia Sinica
2009-2012 Postdoc and Assistant Researcher, Molecular, Cell, and Developmental Biology, UCLA
2008 Postdoc, Oxford Centre for Integrative Systems Biology, Oxford University
2008 D.Phil, Statistics (Computational Biology), Oxford University

Pao-Yang Chen 陳柏仰

Principal Investigator

MA Children's Book Illustration
Anglia Ruskin University

Nien Yang 楊念蓁

Lab Manager (02) 2787-1139

PhD Molecular Biology
National Chung Hsing University

Ming-Ren Yen 嚴明仁

Postdoctoral Researcher

TIGP Bioinformatics Program
NTU & Academia Sinica

Yu-Chun Huang 黃郁珺

PhD student

Genome and Systems Biology
National Taiwan University

Jo-Wei Hsieh 謝若微

PhD student

MSc Ecology and Conservation
University of Aberdeen

Pei-Yu Lin 林蓓郁

Research Assistant

MS Institute of Plant Biology
National Taiwan University

Chih-Hung Hsieh 謝誌紘

Research Assistant

PhD Statistics
University of Edinburgh

Ya-Ting Chang 張雅婷

Postdoctoral Researcher


Undergraduate Researchers

Department of Medical Laboratory Science And Biotechnology
National Cheng Kung University


Undergraduate Researcher



Google Scholar

ORCID iD iconhttps://orcid.org/0000-0002-7402-3075

Journal Articles


Fu-Yu Hung, Chen Chen, Ming-Ren Yen, Jo-Wei Allison Hsieh, Chenlong Li, Yuan-Hsin Shih, Fang-Fang Chen, Pao-Yang Chen*, Yuhai Cui*, Keqiang Wu* (2020) The expression of long noncoding RNAs is associated with H3Ac and H3K4me2 changes regulated by the HDA6-LDL1/2 histone modification complex in Arabidopsis NAR Genomics and Bioinformatics Vol 2, Issue 3, lqaa066

Hong Zhu, Pao-Yang Chen, Silin Zhong, Christopher Dardick, Ann Callahan, Yong-Qiang An, Steve van Nocker, Yingzhen Yang, Gan-Yuan Zhong, Albert Abbott, Zongrang Liu (2020) Thermal-responsive genetic and epigenetic regulation of DAM cluster controlling dormancy and chilling requirement in peach floral buds Horticulture Research 7, 114

Jo-Wei Allison Hsieh, Ming-Ren Yen, Pao-Yang Chen (2020) Epigenomic regulation of OTU5 in Arabidopsis thaliana Genomics 112(5): 3549-3559

Chin-Sheng Teng, Bing-Heng Wu, Ming-Ren Yen, Pao-Yang Chen (2020) MethGET: web-based bioinformatics software for correlating genome-wide DNA methylation and gene expression BMC Genomics 21:375 Website

Sheng-Yao Su, I-Hsuan Lu, Wen-Chih Cheng, Wei-Chun Chung, Pao-Yang Chen, Jan-Ming Ho, Shu-Hwa Chen, Chung-Yen Lin (2020) EpiMOLAS: an intuitive web-based framework for genome-wide DNA methylation analysis BMC Genomics 21,163 Website

Emilie debladis, Tzuu-Fen Lee, Yan-Jiun Huang, Jui-Hsien Lu, Sandra Mathioni, Marie-Christine Carpentier, Christel Llauro, Davy Pierron, Delphine Mieulet, Emmanuel Guiderdoni, Pao-Yang Chen, Blake Meyers, Olivier Panaud, Eric Lasserre (2020) Construction and characterization of a knock-down RNA interference line of OsNRPD1 in rice (Oryza sativa ssp. Japonica cv. Nipponbare) Philosophical Transactions of the Royal Society B 375:20190338


Yang Jie, Lianyu Yuan, Ming‐Ren Yen, Feng Zheng, Rujun Ji, Tao Peng, Dachuan Gu, Songguang Yang, Yuhai Cui, Pao‐Yang Chen, Keqiang Wu, Xuncheng Liu (2019) SWI3B and HDA6 are Required for Transposon Silencing in Arabidopsis The Plant Journal doi:10.1111/tpj.14666

You-Yuan Pang, Jui-Hsien Lu, Pao-Yang Chen (2019) Behavioral Epigenetics: Perspectives based on Experience-Dependent Epigenetic Inheritance Epigenomes 3(3), 18
Nien's artwork for cover page :

Phuong Nguyen Tran, Ming-Ren Yen, Chen-Yu Chiang, Hsiao-Ching Lin*, Pao-Yang Chen* (2019) Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi Applied Microbiology and Biotechnology Vol 103, Issue 8, 3277-3287

Ta-Ching Chen, Pin-Yi She, Dong Feng Chen, Jui-Hsien Lu, Chang-Hao Yang, Ding-Siang Huang, Pao-Yang Chen, Chen-Yu Lu, Kin-Sang Cho, Hsin-Fu Chen, Wei-Fang Su (2019) Polybenzyl glutamate biocompatible scaffold promotes the efficiency of retinal differentiation toward retinal ganglion cell lineage from human induced pluripotent stem cells International Journal of Molecular Sciences 20(1), 178


Jie Hou, Xiaowen Shi, Chen Chen, Soliman Islam, Adam F. Johnson, Tatsuo Kanno, Bruno Huettel, Ming-Ren Yen, Fei-Man Hsu, Tieming Ji, Pao-Yang Chen, Marjori Matzke, Antonius J.M. Matzke, Jianlin Cheng, James A. Birchler (2018) Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.1807796115 Commentary-Genomic Balance and Speciation

Fei-Man Hsu, Moloya Gohain, Archana Allishe, Yan-Jiun Huang, Jo-Ling Liao, Lin-Yun Kuang and Pao-Yang Chen (2018) Dynamics of the Methylome and Transcriptome during the Regeneration of Rice Epigenomes 2(3), 14

Yu Yuan Huang, Yan-Jiun Huang, Pao-Yang Chen (2018) BS-Seeker3: Ultrafast pipeline for bisulfite sequencing BMC Bioinformatics 19:111

Fei-Man Hsu, Chung-Ju Rachel Wang* and Pao-Yang Chen* (2018) Reduced Representation Bisulfite Sequencing in Maize Bio-protocol 8(6): e2778. DOI: 10.21769/BioProtoc.2778

Pearl Chang, Moloya Gohain, Ming-Ren Yen, Pao-Yang Chen (2018) Computational Methods for Assessing Chromatin Hierarchy Computational and Structural Biotechnology Journal https://doi.org/10.1016/j.csbj.2018.02.003

Pearl Chang, Yu-Fang Tseng, Pao-Yang Chen* and Chung-Ju Rachel Wang* (2018) Using flow cytometry to isolate maize meiocytes for next generation sequencing: A time and labor efficient method Current Protocols in Plant Biology https://doi.org/10.1002/cppb.20068

Yu Tao☨, Ming-Ren Yen☨, Tsotne Chitiashvili, Haruko Nakano, Rachel Kim, Linzi Hosohama, Yao Chang Tan, Atsushi Nakano, Pao-Yang Chen*, Amander T Clark* (2018) TRIM28-regulated transposon repression is required for human germline competency and not primed or naïve human pluripotency Stem Cell Reports Volume 10, Issue 1, p243–256 . (☨ co-first, * co-corresponding authors)

Fei-Man Hsu, Moloya Gohain, Pearl Chang, Jui-Hsien Lu, Pao-Yang Chen (2018) Bioinformatics of Epigenetic Data Generated from Next-Generation Sequencing Epigenetics in Human Disease, 2nd edition, Elsevier Vol.6 in Translational Epigenetics 65-106


Jer-Young Lin, Brandon Le, Min Chen, Kelli F. Henry, Jungim Hur, Tzung-Fu Hsieh, Pao-Yang Chen, Julie M. Pelletier, Matteo Pellegrini, Robert L. Fischer, John J. Harada, Robert B. Goldberg (2017) Similarity between soybean and Arabidopsis seed methylomes and loss of non-CG methylation does not affect seed development Proceedings of the National Academy of Sciences doi: 10.1073/pnas.1716758114

Ming-Ren Yen, Der-Fen Suen, Fei-Man Hsu, Yi-Hsiu Tsai, Hongyong Fu, Wolfgang Schmidt*, and Pao-Yang Chen* (2017) Deubiquitinating enzyme OTU5 contributes to DNA methylation patterns and is critical for phosphate nutrition signals Plant Physiology 175 (4) 1826-1838

Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, Fung-Rong Hu (2017) Vascular hypoperfusion in acute optic neuritis is a potentially new neurovascular model for demyelinating diseases PLoS ONE 12(9): e0184927

Huei-Mei Hsieh, Mei-Chu Chung, Pao-Yang Chen, Fei-Man Hsu, Wen-Wei Liao, Ai-Ning Sung, Chun-Ru Lin, Chung-Ju Wang, Yu-Hsin Kao, Mei-Jane Fang, Chi-Yung Lai, Chieh-Chen Huang, Jyh-Ching Chou, Wen-Neng Chou, Bill Chia-Han Chang and Yu-Ming Ju (2017) A termite symbiotic mushroom maximizing sexual activity at growing tips of vegetative hyphae. Botanical Studies 58: 39

Fei-Man Hsu, Ming-Ren Yen, Chi-Ting Wang, Chien-Yu Lin, Chung-Ju Rachel Wang* and Pao-Yang Chen* (2017) Optimized reduced representation bisulfite sequencing reveals tissue-specific mCHH islands in maize. Epigenetics & Chromatin 10:42 Gitlab

Pao-Yang Chen☨, Alison Chu☨, Wen-Wei Liao, Liudmilla Rubbi, Carla Janzen, Fei-Man Hsu, Amit Ganguly, Shanthie Thamotharan, Matteo Pelligrini, Sherin Devaskar (2017) Prenatal growth patterns and birthweight are associated with differential DNA methylation and gene expression of cardiometabolic risk genes in human placentas Reproductive Sciences 1-17

Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen and Cheng-Fu Kao (2017) H2B ubiquitylation and the histone chaperone Asf1 cooperatively mediate the formation and maintenance of heterochromatin silencing Nucleic Acids Research Vol 45, 14, 8225–8238

Fei-Man Hsu, Pao-Yang Chen (2017) Game theory in epigenetic reprogramming: Comment on: “Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition” by Qian Wang et al. Physics of Life Reviews 20:143-145


Sheng-Yao Su, Shu-Hwa Chen, I-Hsuan Lu, Yih-Shien Chiang, Yu-Bin Wang, Pao-Yang Chen* and Chung-Yen Lin* (2016) TEA: the epigenome platform for Arabidopsis methylome study. BMC Genomics 17:3326 Website

Joseph Hargan-Calvopina, Sara Taylor, Helene Cook, Zhongxun Hu, Serena A. Lee, Ming-Ren Yen, Yih-Shien Chiang, Pao-Yang Chen, Amander T. Clark (2016) Stage-Specific Demethylation in Primordial Germ Cells Safeguards against Precocious Differentiation. Developmental Cell 39 1:12

Wai-Shin Yong☨, Fei-Man Hsu☨, Pao-Yang Chen (2016) Profiling genome-wide DNA methylation. Epigenetics & Chromatin 9:26

Colin Flinders☨, Larry Lam☨, Liudmilla Rubbi, Roberto Ferrari, Sorel Fitz-Gibbon, Pao-Yang Chen, Michael Thompson, Heather Christofk, David B Agus, Daniel Ruderman, Parag Mallick and Matteo Pellegrini (2016) Epigenetic changes mediated by polycomb repressive complex 2 and E2a are associated with drug resistance in a mouse model of lymphoma. Genome Medicine 8:54

Fei-Man Hsu☨, Wai-Shin Yong☨, Pao-Yang Chen (2016) Views on Profiling Genomewide DNA Methylation and Crop Methylomes. Crop, Environment & Bioinformatics 13:39-51


Fei-Man Hsu, Amander T Clark, Pao-Yang Chen (2015) Epigenetic reprogramming in the mammalian germline.Oncotarget DOI: 10.18632/oncotarget.6206

Wen-Wei Liao☨, Ming-Ren Yen☨, Evaline Ju, Fei-Man Hsu, Larry Lam, Pao-Yang Chen (2015) MethGO: a comprehensive tool for analyzing whole genome bisulte sequencing data. BMC Genomics 16(Suppl 12):S11 Software

Gkountela, Kelvin Zhang, Tiasha Shaq, Wen-Wei Liao, Joseph Hargan-Calvopina, Pao-Yang Chen*, Amander T Clark* (2015) DNA Demethylation Dynamics in the Human Prenatal Germline. Cell 161:1-12 (co-corresponding authors)

Taku Sasaki, Tatsuo Kanno, Shih-Chieh Liang, Pao-Yang Chen, Wen-Wei Liao, Wen-Dar Lin, Antonius J.M. Matzke* and Marjori Matzke* (2015) An Rtf2 domain-containing protein influences pre-mRNA splicing and is essential for embryonic development in Arabidopsis thaliana. Genetics doi: 10.1534/genetics.115.176438


Pao-Yang Chen☨, Barbara Montanini☨, Wen-Wei Liao, Marco Morselli, Artur Jaroszewicz, David Lopez, Simone Ottonello and Matteo Pellegrini (2014) A comprehensive resource of genomic, epigenomic and transcriptomic sequencing data for the black truffe Tuber melanosporum. GigaScience 3:25

Barbara Montanini☨, Pao-Yang Chen☨, Marco Morselli, Artur Jaroszewicz, David Lopez, Francis Martin, Simone Ottonello and Matteo Pellegrini. (2014) Non-exhaustive DNA methylation-mediated transposon silencing in the black truffle genome, a complex fungal genome with massive repeat element content. Genome Biology 15:411

Negar M Ghahramani, Tuck C Ngun, Pao-Yang Chen, Yuan Tian, Sangitha Krishnan, Stephanie Muir, Liudmilla Rubbi, Arthur P Arnold, Geert J de Vries, Nancy G Forger, Matteo Pellegrini, Eric Vilain (2014) The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging. Biol Sex Differ 5:8

Sasaki T, Lee TF, Liao, Wen-Wei, Naumann U, Liao Joling, Eun CH, Huang YY, Fu JL, Pao-Yang Chen, Meyers BC, Matzke AJM, and Matzke M. (2014) Distinct and concurrent pathways of Pol II and Pol IV-dependent siRNA biogenesis at a repetitive trans-silencer locus in Arabidopsis thaliana, The Plant Journal doi: 10.1111/tpj.12545


Guo W, Fiziev P, Yan W, Cokus S, Sun X, Zhang MQ, Pao-Yang Chen* & Pellegrini M.* (2013) BS-Seeker2: a versatile aligning pipeline for bisulfite sequencing data. BMC Genomics 14(1): 774 (co-corresponding authors) Github

Pao-Yang Chen, Amit Ganguly, Liudmilla Rubbi, Luz D. Orozco, Marco Morselli, Davin Ashraf, Artur Jaroszewicz, Suhua Feng, Steve E. Jacobsen, Atsushi Nakano, Sherin U. Devaskar, and Matteo Pellegrini (2013) Intra-uterine calorie restriction affects placental DNA methylation and gene expression, Physiol. Genomics doi:10.1152

J. Vincent, Y. Huang, Pao-Yang Chen, S. Feng, J.. Calvopia, K. Nee, S. Lee, T. Le, A. Yoon, K. Faull, G. Fan, A. Rao, S. Jacobsen, M. Pellegrini, and A. Clark (2013) Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells, Cell Stem Cell 12(4):470-8

Before 2013

Pao-Yang Chen, M. Pellegrini (2012) Methylomes, Epigenetic Regulation and Epigenomics from the Encyclopedia of Molecular Cell Biology and Molecular Medicine, pp. 815-837, UK: John Wiley & Sons, Inc. (invited review)

Pao-Yang Chen, S. Feng, J. Joo, S. Jacobsen, M. Pellegrini (2011) A comparative analysis of DNA methylation across human embryonic stem cell lines, Genome Biology 12:R62 (highly accessed)

Shota Atsumi, Tung-Yun Wu, I. Machado, W. Huang, Pao-Yang Chen, Matteo Pellegrini, James C Liao (2010) Evolution, genomic analysis, and reconstruction of isobutanol tolerance in Escherichia coli. Nature-EMBO Molecular Systems Biology 6: 499

R. Chodavarapu, S. Feng, Y. Bernatavichute, Pao-Yang Chen, H. Stroud, Y. Yu, J. Hetzel, F. Kuo, J. Kim, S. Cokus, D. Casero, M. Bernal, P. Huijser, A. Clark, U. Krmer, S. Merchant, X. Zhang, S. Jacobsen, M. Pellegrini (2010) Relationship between nucleosome positioning and DNA methylation. Nature 466, 388-392

S. Feng, S. Cokus, X. Zhang, Pao-Yang Chen, M. Bostick, M. Goll, J. Hetzel, J. Jain, S. Strauss, M. Halpern, C. Ukomadu, K. Sadler, M. Pellegrini, S. Jacobsen (2010) Conservation and divergence of plant and animal methylation patterning. Proceedings of the National Academy of Sciences, 11;107(19):8689-94

Pao-Yang Chen, S. Cokus, M. Pellegrini, (2010) BS Seeker: precise mapping for bisulfite sequencing. BMC Bioinformatics 11: 203 (highly accessed)

R. Hamer*, Pao-Yang Chen*, J. Armitage, G. Reinert, C. Deane (2010) Deciphering chemotaxis pathways using cross species comparisons. BMC Systems Biology, 4: 3 (co-furst authors)

Pao-Yang Chen, C. Deane, G. Reinert (2008) Predicting and validating protein interactions using network structure. PLoS Computational Biology 4(7): e1000118

Pao-Yang Chen, C. Deane, G. Reinert (2007) A statistical approach using network structure in the prediction of protein characteristics. Bioinformatic 23 (17): 2314-2321

C. Lin, S. Chen, C. Cho, C. Chen, F. Lin, C. Lin, Pao-Yang Chen, C. Lo, C. Hsiung, (2006) Fly-DPI: database of protein interactomes for D. melanogaster in the approach of systems biology.BMC Bioinformatics 7 (5) S18

C. Chen, C. Lin, C. Cho, L. Wang, C. Chang, Pao-Yang Chen, C. Lo, C. Hsiung, (2005) HP-DPI: Helicobacter Pylori Database of Protein Interactomes, a combined experimental and inferring interactions. Bioinformatics, 21(7):1288-1290

Y. Chen, J. Chen, K. Richard, Pao-Yang Chen, D. Christiani, (2004) Lung adenocarcinoma and human papillomavirus infection. Cancer15;101(6):1428-36

C. Hwu, C. Hsiao, S. Kuo, K. Wu, C. Ting, T. Quertermous, B, Rodriguez, I. Chen, J. Grove, Pao-Yang Chen, L. Ho, (2004) Physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. Blood Pressure 13 (6): 355-361 (Selected in the Outstanding Thesis Collection by Ministry of National Defense, Taiwan)

Ching Liu and Pao-Yang Chen (1999) Mapping and analysis of Quantitative Trait Loci (QTL) for Poisson distributed data. Chinese Agronomy Journal 9(3):127-141


Epigenetic discrimination of DNA United States Patent Application 16/325097

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中央研究院 植物暨微生物學研究所 陳柏仰研究室 R315 (Office)/ R316 (LAB)


R315 (Office)/ R316 (LAB), Institute of Plant and Microbial Biology, Academia Sinica
128 Sec 2, Academia Rd, Nankang, Taipei City, Taiwan