In eukaryotic cells, nuclear DNA is packaged into chromatin, of which the nucleosome is the most basic unit, formed by ~200 base pairs (bp) of DNA wrapped around a protein core of histones. In addition to genetic information carried by DNA, a large amount of epigenetic information is carried by chromatin, mainly in the form of various post-translational modifications (PTMs) of histones. Replication of nuclear DNA is tightly coupled with histone deposition and nucleosome assembly. Various histone-modifying enzymes, including acetyltransferases, deacetylases, and methyltransferases, play important roles in DNA replication. Nonetheless, the understanding of how the duplication of genetic and epigenetic information is coordinated is limited, as epigenetic factors affecting replication elongation have so far been poorly characterized. 

Since 2011, Dr. MIAO Wei's lab (Institute of hydrobiology, Chinese Academy of Sciences) and Dr. LIU Yifan's lab (University of Michigan) started a cooperation of studying the relationship between the epigenetic factors and DNA replication. Based on the identification of the TRX1 gene (a histone methyltransferase) and investigation of its biological function in histone H3 lysine 27 monomethylation (H3K27me1) of Tetrahymena cells, they found that TXR1 gene deletion resulted in severe DNA replication stress, including the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses.  

Using the paired-end Illumina sequencing, they found ssDNA enriched in the replication origins, and established new genome-wide DNA replication origins identification method. In addition, they demonstrated the interaction between TXR1 and proliferating cell nuclear antigen (PCNA) which directly involved in DNA replication and play important role in replication elongation. These findings support a conserved pathway through which H3K27me1 facilitates replication elongation.  

This study was the first discovery between the H3K27me1 and DNA replication elongation in unicellular organisms. It confirmed the existence of a conserved pathway through which H3K27me1 facilitates replication elongation, and gave important clues in DNA replication origin identification and reorganization.

The study was published in the journal GENES & DEVELOPMENT on July 24, 2013 entitled “Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation " (http://genesdev.cshlp.org/content/early/2013/07/22/gad.218966.113).