Currently, Chuanhe Yu is an Assistant Professor at the Hormel Institute, University of Minnesota. His research interests are genome instability and epigenetic regulation mechanisms. Dr. Yu received his undergraduate and master’s degree from Sun Yat-Sen University in China.  

During his Ph.D. training at Iowa State University, he found that transposable elements can induce chromosome breakage and major chromosome rearrangements via alternative transposition mechanisms in maize. 

After his graduate studies, Dr. Yu joined the National Cancer Institute at Frederick, Maryland, to study the mating-type switch mechanism in fission yeast. 

In 2012, Dr. Yu started his postdoctoral training in the field of epigenomics at Mayo Clinic. He developed a new technique we named eSPAN, which enables the analysis of selective binding of proteins to leading and lagging strands of replicating DNA. 

Currently, he is investigating the fundamental mechanisms of epigenetic inheritance in budding yeast, including how parental histones are transferred to new DNA and how histone marks are transferred to the daughter cells.

Education

• PhD: Genetics, Iowa State University, Ames, Iowa, 2004–2009
• MS: Biochemistry and Molecular Biology, Sun Yat-Sen University, Guangzhou, China, 2000–2003
• BS: Microbiology, Sun Yat-Sen University, Guangzhou, China, 1996–2000

Research Interests

I am interested in DNA replication-coupled epigenetic inheritance. One of the major unanswered questions in the field of epigenetic inheritance is how parental histones are transferred onto replicating DNA. Parental histone (H3-H4)2 tetramers have been proposed to randomly segregate between leading and lagging strands of DNA replication forks. 

However, we found that the parental histone (H3-H4)2 tetramers consistently enriched at lagging strands of DNA replication in budding yeast. Intriguingly, in cells depleted of Dpb3 and Dpb4, which are non-catalytic subunits of the leading strand DNA polymerase, Pol ε, the bias of parental nucleosome segregation to the lagging strand was markedly enhanced. Pol ε thus appears to mediate the recruitment of parental nucleosomes to the leading strand. 

We also discovered that parental H3-H4 tetramers bind to MCM helicase subunit (Mcm2) and are then transferred to the lagging strand by the Mcm2-Ctf4-Pol α complex for nucleosome assembly. While the mitotic cell cycle was not much affected by the asymmetric nucleosome partitioning, we found that mating-type gene silencing was significantly disturbed in the Dpb3/Dpb4 and Mcm2 mutant budding yeast cells. 

These studies thus suggest that parental nucleosome segregation is determined by a balance of replisome-intrinsic histone chaperone activities. Modulation of individual histone chaperone activities at the fork may therefore provide a potential mechanism for the asymmetric distribution of epigenetic marks to determine cell fate in development. Now we are exploring other chromatin factors that regulate the epigenetic inheritance process.

Primary Research Areas

• Epigenetics
• Genomics
• Genome stability

Awards

• Mayo-Kendall Postdoctoral Fellowship in Biochemistry, Mayo Clinic, USA (2015-2017)
• D. Honored with Research Excellence, Iowa State University, USA (2009)

Publications

1. Yang X, Karri S, Yu C. Asymmetric inheritance of parental histones leads to differentiation defects in mouse embryonic stem cells. Innov Life 2024; 2. PMCID:38601056 

2. Tian C, Zhang Q, Jia J, Zhou J, Zhang Z, Karri S, Jiang J, Dickinson Q, Yao Y, Tang X, Huang Y, Guo T, He Z, Liu Z, Gao Y, Yang X, Wu Y, Chan KM, Zhang D, Han J, Yu C, Gan H. DNA polymerase delta governs parental histone transfer to DNA replication lagging strand. Proc Natl Acad Sci U S A 2024; 121: e2400610121. PMCID:38713623 

3. Karri S, Yang Y, Zhou J, Dickinson Q, Jia J, Huang Y, Wang Z, Gan H, Yu C. Defective transfer of parental histone decreases frequency of homologous recombination by increasing free histone pools in budding yeast. Nucleic Acids Res 2024. PMCID:38554108 

4. Karri S, Dickinson Q, Jia J, Yang Y, Gan H, Wang Z, Deng Y, Yu C. The role of hexokinases in epigenetic regulation: altered hexokinase expression and chromatin stability in yeast. Epigenetics Chromatin 2024; 17: 27. PMCID:39192292 

5. Jia J, Yu C. The Role of the MCM2-7 Helicase Subunit MCM2 in Epigenetic Inheritance. Biology (Basel) 2024; 13. PMCID:39194510 

6. Wen Q, Zhou J, Tian C, Li X, Song G, Gao Y, Sun Y, Ma C, Yao S, Liang X, Kang X, Wang N, Yao Y, Wang H, Liang X, Tang J, Offer SM, Lei X, Yu C, Liu X, Liu Z, Wang Z, Gan H. Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation. Nat Genet 2023; 55: 1555-66. PMCID:37666989 

7. Tian C, Zhou J, Li X, Gao Y, Wen Q, Kang X, Wang N, Yao Y, Jiang J, Song G, Zhang T, Hu S, Liao J, Yu C, Wang Z, Liu X, Pei X, Chan K, Liu Z, Gan H. Impaired histone inheritance promotes tumor progression. Nat Commun 2023; 14: 3429. PMCID:37301892 

8. Wang D, Yu C, Zhang J, Peterson T. Excision and reinsertion of Ac macrotransposons in maize. Genetics 2022. PMCID:35471241 

9. Serra-Cardona A, Duan S, Yu C, Zhang Z. H3K4me3 recognition by the COMPASS complex facilitates the restoration of this histone mark following DNA replication. Sci Adv 2022; 8: eabm6246. PMCID:35544640 

10. Serra-Cardona A, Yu C, Zhang X, Hua X, Yao Y, Zhou J, Gan H, Zhang Z. A mechanism for Rad53 to couple leading- and lagging-strand DNA synthesis under replication stress in budding yeast. Proc Natl Acad Sci U S A 2021; 118. PMCID:34531325 

11. Yang Y, Yu C. Liquid phase condensation directs nucleosome epigenetic modifications. Signal Transduct Target Ther 2020; 5: 64. PMCID:32376821 

12. Yu C, Gan H, Zhang Z. Strand-Specific Analysis of DNA Synthesis and Proteins Association with DNA Replication Forks in Budding Yeast. Methods Mol Biol 2018; 1672: 227-38. PMCID:29043628 

13. Yu C, Gan H, Serra-Cardona A, Zhang L, Gan S, Sharma S, Johansson E, Chabes A, Xu RM, Zhang Z. A mechanism for preventing asymmetric histone segregation onto replicating DNA strands. Science 2018; 361: 1386-9. PMCID:30115745 

14. Li S, Xu Z, Xu J, Zuo L, Yu C, Zheng P, Gan H, Wang X, Li L, Sharma S, Chabes A, Li D, Wang S, Zheng S, Li J, Chen X, Sun Y, Xu D, Han J, Chan K, Qi Z, Feng J, Li Q. Rtt105 functions as a chaperone for replication protein A to preserve genome stability. EMBO J 2018; 37. PMCID:30065069 

15. Gan H, Serra-Cardona A, Hua X, Zhou H, Labib K, Yu C, Zhang Z. The Mcm2-Ctf4-Polalpha Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands. Mol Cell 2018; 72: 140-51 e3. PMCID:30244834 

16. Yu C, Gan H, Zhang Z. Both DNA Polymerases delta and epsilon Contact Active and Stalled Replication Forks Differently. Mol Cell Biol 2017; 37. PMCID:28784720 

17. Gan H, Yu C, Devbhandari S, Sharma S, Han J, Chabes A, Remus D, Zhang Z. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress. Mol Cell 2017; 68: 446-55 e3. PMCID:29033319 

18. Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, Farrugia G, Ordog T, Zhang Z. Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall. Mol Cell 2014; 56: 551-63. PMCID:25449133 

19. Yu C, Bonaduce MJ, Klar AJ. Defining the epigenetic mechanism of asymmetric cell division of Schizosaccharomyces japonicus yeast. Genetics 2013; 193: 85-94. PMCID:23150598 

20. Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 2013; 27: 985-90. PMCID:23603901 

21. Yu C, Bonaduce MJ, Klar AJ. Going in the right direction: mating-type switching of Schizosaccharomyces pombe is controlled by judicious expression of two different swi2 transcripts. Genetics 2012; 190: 977-87. PMCID:22209903 

22. Yu C, Bonaduce MJ, Klar AJ. Remarkably high rate of DNA amplification promoted by the mating-type switching mechanism in Schizosaccharomyces pombe. Genetics 2012; 191: 285-9. PMCID:22377633 

23. Yu C, Zhang J, Peterson T. Genome rearrangements in maize induced by alternative transposition of reversed ac/ds termini. Genetics 2011; 188: 59-67. PMCID:21339479 

24. Yu C, Zhang J, Pulletikurti V, Weber DF, Peterson T. Spatial configuration of transposable element Ac termini affects their ability to induce chromosomal breakage in maize. Plant Cell 2010; 22: 744-54. PMCID:20228246