Stress triggers global histone synthesis in the liver
- 1Stanford University
Abstract
Despite extensive drug development targeting DNA synthesis, there have been few efforts to inhibit histone synthesis, which occurs jointly with DNA synthesis in S-phase. A major roadblock is the lack of tools to quantitatively measure histone synthesis due to the high abundance and stability of histone proteins. Here we present chemical labeling methodologies to produce the first in vivo measurements of histone synthesis rates. Under basal conditions, histone synthesis tracks closely with tissue proliferation. However, multiple systemic and liver-specific stresses induce a previously uncharacterized surge of hepatocyte nucleosome production that is uncoupled from DNA replication. Tracing of newly synthesized nucleosomes detected promoter deposition, which was required to buffer transcriptional output. These results may inform strategies to modulate histone production to influence stress responses or disease.
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BibTeX
@misc{rajkumar2026stress,
title = {{Stress triggers global histone synthesis in the liver}},
author = {S. Rajkumar and L. Vumma and J. Naidoo and M. Zhu and I. Durdana and S. V. Chandrasekar and C. Golder and H. Goar and W. K. Kicinski and R. Gamuyao and Y. Wei and H. Zhu and S. J. Patel and J. M. Ready and M. Buszczak and J. J. Gruber},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753600},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753600v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Stress triggers global histone synthesis in the liver
AU - S. Rajkumar
AU - L. Vumma
AU - J. Naidoo
AU - M. Zhu
AU - I. Durdana
AU - S. V. Chandrasekar
AU - C. Golder
AU - H. Goar
AU - W. K. Kicinski
AU - R. Gamuyao
AU - Y. Wei
AU - H. Zhu
AU - S. J. Patel
AU - J. M. Ready
AU - M. Buszczak
AU - J. J. Gruber
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753600
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753600v1
AB - Despite extensive drug development targeting DNA synthesis, there have been few efforts to inhibit histone synthesis, which occurs jointly with DNA synthesis in S-phase. A major roadblock is the lack of tools to quantitatively measure histone synthesis due to the high abundance and stability of histone proteins. Here we present chemical labeling methodologies to produce the first in vivo measurements of histone synthesis rates. Under basal conditions, histone synthesis tracks closely with tissue proliferation. However, multiple systemic and liver-specific stresses induce a previously uncharacterized surge of hepatocyte nucleosome production that is uncoupled from DNA replication. Tracing of newly synthesized nucleosomes detected promoter deposition, which was required to buffer transcriptional output. These results may inform strategies to modulate histone production to influence stress responses or disease.
ER -