Recycling represents one of the most important strategies to keep the planet clean and green for generations to come. Used paper, metal, and plastic and other assorted detritus generally encounter a second use, but can we recycle the histone proteins that help to package our DNA and maintain cell-type-specific transcriptional programs?
A lean, clean, and green team led by Anja Groth (University of Copenhagen, Denmark) couldn´t let such a tantalizing question goes to “waste”, and so they developed a new genome-wide technique (ChOR-seq) to analyze chromatin occupancy after DNA replication by next-generation sequencing. ChOR-seq tracks recycling of “old” histones and directly measures the replication-dependent displacement of pre-existing histone modifications by employing a combination of pulse labeling of replicating DNA with a nucleotide analog and the knowledge that newly synthesized histones lack tri-methylation modifications at the time of deposition.
Using this newly developed approach, the team now demonstrates that our cells can indeed recycle their histone proteins during DNA replication to keep their histone modification landscapes in a pristine condition for generations to come! Furthermore, this eco-friendly study also suggests that the incorporation and modification of new histone proteins may induce epigenome fluctuations across the cell cycle that underlies cellular heterogeneity.
Here are all the details on this recycling report from Reverón-Gómez and colleagues:
- Histone recycling permits the reproduction of positional information regarding trimethylated lysine modifications on histone H3 on newly synthesized DNA in transcriptionally repressed and active genome regions
- De novo histone methylation restores H3K4me3 and H3K27me3 levels during the cell cycle at sites demarcated by parental histones
- A substantial increase in H3K4me3 and H3K27me3 signal intensity during chromatin maturation argues that de novo tri-methylation occurs in a manner uncoupled from DNA replication
- The kinetics of restoration depends on the specific modification and the locus involved, and differences between these kinetic rates may underlie cell-to-cell heterogeneity
- Establishment of H3K4me3 on new histones occurs by G2 (before mitosis) while the restoration of repressive marks (H3K27me3 and H3K9me3) follows in G1 of the next cell cycle
- Transcriptional status and CpG content determine H3K4me3 restoration kinetics, while PRC2 (polycomb repressive complex 2) occupancy influences H3K27me3 restoration
Overall, recycling aids the histone modification landscape to withstand the disruption of DNA replication and ensures that daughter strands of DNA faithfully inherit positional information of histone marks. The authors now hope to shift their focus from histone H3 to histones H2A–H2B to analyze transmission patterns during DNA replication and to assess the symmetrical nature of distribution of modified histones on the two daughter stands.
For now, keep it green and pristine with this eco-friendly (and freely available online!) new study from Molecular Cell, August 2018!