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Cheng-Fu Kao, Ph. D. 高承福 博士
Research Fellow
Institute of Cellular and Organismic Biology, Academia Sinica
中央研究院 細胞與個體生物學研究所 研究員
Email: ckao@gate.sinica.edu.tw
Epigenetic Control of Cardiomyocyte State Maintains Adult Heart Homeostasis
Adult cardiomyocytes (CMs) are terminally differentiated cells that must preserve their specialized transcriptional and structural states to sustain lifelong cardiac function. However, the epigenetic mechanisms that stabilize CM identity and limit maladaptive plasticity remain poorly understood. Here, we identify the histone H2B ubiquitin ligase RNF20 as a key chromatin regulator that maintains adult CM state and heart homeostasis.
Using an inducible CM-specific RNF20 knockout model, we show that loss of RNF20 impairs cardiac function, promotes interstitial fibrosis, and leads to premature death. Single-nucleus RNA sequencing reveals that RNF20-deficient CMs exhibit transcriptional regression toward immature states, marked by fetal gene reactivation and sarcomere disassembly, without evidence of productive proliferation.
Mechanistically, RNF20 loss induces partial YAP pathway activation, with enhanced nuclear YAP localization in CMs. Increased Agrn expression and reduced connexin 43 likely contribute to this altered YAP signaling. Our findings demonstrate that RNF20-mediated chromatin regulation preserves adult CM identity and prevents maladaptive dedifferentiation.
This work highlights the broader principle that epigenetic control is critical for stabilizing differentiated cell states. It provides new insights into how chromatin dynamics regulate postnatal cell fate stability, with implications for understanding tissue homeostasis and informing regenerative strategies.
Position
2022- Deputy Director, Institute of Cellular and Organismic Biology, Academia Sinica
2020- Research Fellow, Institute of Cellular and Organismic Biology, Academia Sinica
Education
2002 – 2006 Postdoctoral training with Mary Ann Osley at University of New Mexico
1997 – 2002 Ph. D., Department of Biochemistry University of Edinburgh
1991 – 1993 M. A., Depart of Nutrition, Fu-Jen Catholic University, Taiwan
1987 – 1991 B.S., Depart of Nutrition, Fu-Jen Catholic University, Taiwan
Expertise
Chromatin and Epigenetic Modifications in Genome Function and Cell Identity
Selected Publications
Lin CY, Chang YM, Tseng HY, Shih YL, Yeh HH, Liao YR, Hsu CL, Chen CC, Yan YT, Kao CF. Epigenetic regulator RNF20 underlies temporal hierarchy of gene expression to regulate postnatal cardiomyocyte polarization. Cell Rep. 2023 Nov 28;42(11):113416. doi: 10.1016/j.celrep.2023.113416.
Huang JH, Liao YR, Lin TC, Tsai CH, Lai WY, Chou YK, Leu JY, Tsai HK, Kao CF. iTARGEX analysis of yeast deletome reveals novel regulators of transcriptional buffering in S phase and protein turnover. Nucleic Acids Res. 2021 Jul 21;49(13):7318-7329. doi: 10.1093/nar/gkab555.
Hsu CL, Chong SY, Lin CY, Kao CF. Histone dynamics during DNA replication stress. J Biomed Sci. 2021 Jun 19;28(1):48. doi: 10.1186/s12929-021-00743-5.
Hsu CL, Lo YC, Kao CF. H3K4 Methylation in Aging and Metabolism. Epigenomes. 2021 Jun 18;5(2):14. doi: 10.3390/epigenomes5020014.
Chong SY, Cutler S, Lin JJ, Tsai CH, Tsai HK, Biggins S, Tsukiyama T, Lo YC and Kao CF. H3K4 methylation at active genes mitigates transcription-replication conflicts during replication stress. Nat Commun. 2020 Feb 10;11(1):809. doi: 10.1038/s41467-020-14595-4
Biosketch
Dr. Kao’s laboratory is dedicated to investigating how chromatin modifications influence essential DNA processes—transcription, replication, and repair. While much progress has been made in understanding their role in gene regulation, less is known about how these modifications impact DNA replication and repair. Recognizing this gap, the lab has expanded its efforts to explore the functional roles of chromatin dynamics across these critical processes, aiming to broaden our understanding of genome stability and cellular function.
In addition to this work, the lab has initiated a new research direction focused on how chromatin modifications support the long-term function and homeostasis of terminally differentiated cells. While much of the field emphasizes dramatic epigenetic changes involved in reprogramming and differentiation, such as those in induced pluripotent stem cells (iPSCs), it is equally important to understand the subtle chromatin-based mechanisms that sustain tissue maturation and preserve organ function. Dr. Kao’s team is particularly interested in how these mechanisms contribute to the postnatal development, maturation, and maintenance of cardiomyocytes. Building on emerging evidence that chromatin dynamics govern key aspects of cell physiology, the lab aims to uncover novel insights into cardiac homeostasis and identify pathways that could eventually inform strategies for heart repair and regeneration.
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