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bioRxiv · 10.1101/2024.04.26.591383

Reduced Levels of Lagging Strand Polymerases Shape Stem Cell Chromatin

Snedeker, J.·Davis, B. E. M.·Ranjan, R.·Wooten, M. I.·Blundon, J.·Chen, X.
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Abstract

Stem cells display asymmetric histone inheritance while non-stem progenitor cells exhibit symmetric patterns in the Drosophila male germline lineage. Here, we report that components involved in lagging strand synthesis, such as DNA polymerase and {delta} (Pol and Pol{delta}), have significantly reduced levels in stem cells compared to progenitor cells. Compromising Pol genetically induces the replication-coupled histone incorporation pattern in progenitor cells to be indistinguishable from that in stem cells, which can be recapitulated using a Pol inhibitor in a concentration-dependent manner. Furthermore, stem cell-derived chromatin fibers display a higher degree of old histone recycling by the leading strand compared to progenitor cell-derived chromatin fibers. However, upon reducing Pol levels in progenitor cells, the chromatin fibers now display asymmetric old histone recycling just like GSC-derived fibers. The old versus new histone asymmetry is comparable between stem cells and progenitor cells at both S-phase and M-phase. Together, these results indicate that developmentally programmed expression of key DNA replication components is important to shape stem cell chromatin. Furthermore, manipulating one crucial DNA replication component can induce replication-coupled histone dynamics in non-stem cells in a manner similar to that in stem cells. One Sentence SummaryDelayed lagging strand synthesis regulates asymmetric histone incorporation.

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Snedeker, J., Davis, B. E. M., Ranjan, R., Wooten, M. I., Blundon, J., Chen, X.. 2024-04-29. Reduced Levels of Lagging Strand Polymerases Shape Stem Cell Chromatin. https://doi.org/10.1101/2024.04.26.591383

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