Influence of Histone Acetylation on Chromatin 3D Organization in Drosophila S2 Cells.
6 affiliations
- 1Center for Bio- and Medical Technologies, The Territory of the Skolkovo Innovation Center, Moscow 121205, Russia.
- 2Department of Cellular Genomics, Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
- 3Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
- 4Laboratory of Molecular Genetics of Animals, National Research Centre "Kurchatov Institute", Moscow 123182, Russia.
- 5Laboratory of Analysis of Gene Regulation, National Research Centre "Kurchatov Institute", Moscow 123182, Russia.
- 6Research and Development Department, Medical Company "Genomed", Moscow 115419, Russia.
Abstract
Alterations in histone acetylation are frequently detected in various cancers and neurological diseases. Histone acetylation is known to disrupt both intra- and inter-nucleosomal interactions, but its influence on higher-order chromatin organization has been studied to a lesser extent. In this study, we changed global levels of histone acetylation in Drosophila S2 cells by treatment with trichostatin A (TSA; an inhibitor of histone deacetylases) or with curcumin (an inhibitor of histone acetyltransferases and histone deacetylases). We also performed a knockdown of the main histone deacetylase HDAC1/Rpd3 in S2 cells. According to ChIP-seq analysis, histone H4 pan-acetylation was mostly increased in the active chromatin regions and decreased in the inactive regions after TSA treatment, whereas after curcumin treatment, it changed in the opposite direction. Changes in the level of histone acetylation affect the packaging density of topologically associating domains (TADs), which are the units of higher-order chromatin organization. Importantly, increased histone acetylation leads to decreased packaging density of TADs and vice versa. Moreover, the increased histone acetylation within active TADs enhances their spatial segregation from the inactive ones. Our findings highlight the key role of histone acetylation in determining the 3D organization of chromatin domains, supporting the idea that the separation of active and inactive TADs in Drosophila, at least in part, is mediated by histone acetylation. These results may help to understand how agents such as histone deacetylase inhibitors exert their therapeutic effects in certain cancers and other human diseases.
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BibTeX
@article{kononkova2026influence,
title = {{Influence of Histone Acetylation on Chromatin 3D Organization in Drosophila S2 Cells.}},
author = {Anna D Kononkova and Sergey V Ulianov and Eugenia A Tiukacheva and Elena A Mikhaleva and Semen A Doronin and Victoria A Kobets and Ekaterina E Khrameeva and Sergey V Razin and Yuri Y Shevelyov},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198638},
url = {https://europepmc.org/article/MED/42883883},
note = {CC BY},
}
RIS
TY - JOUR
TI - Influence of Histone Acetylation on Chromatin 3D Organization in Drosophila S2 Cells.
AU - Anna D Kononkova
AU - Sergey V Ulianov
AU - Eugenia A Tiukacheva
AU - Elena A Mikhaleva
AU - Semen A Doronin
AU - Victoria A Kobets
AU - Ekaterina E Khrameeva
AU - Sergey V Razin
AU - Yuri Y Shevelyov
PY - 2026
DA - 2026/09/27
JO - International journal of molecular sciences
DO - 10.3390/ijms27198638
UR - https://europepmc.org/article/MED/42883883
AB - Alterations in histone acetylation are frequently detected in various cancers and neurological diseases. Histone acetylation is known to disrupt both intra- and inter-nucleosomal interactions, but its influence on higher-order chromatin organization has been studied to a lesser extent. In this study, we changed global levels of histone acetylation in Drosophila S2 cells by treatment with trichostatin A (TSA; an inhibitor of histone deacetylases) or with curcumin (an inhibitor of histone acetyltransferases and histone deacetylases). We also performed a knockdown of the main histone deacetylase HDAC1/Rpd3 in S2 cells. According to ChIP-seq analysis, histone H4 pan-acetylation was mostly increased in the active chromatin regions and decreased in the inactive regions after TSA treatment, whereas after curcumin treatment, it changed in the opposite direction. Changes in the level of histone acetylation affect the packaging density of topologically associating domains (TADs), which are the units of higher-order chromatin organization. Importantly, increased histone acetylation leads to decreased packaging density of TADs and vice versa. Moreover, the increased histone acetylation within active TADs enhances their spatial segregation from the inactive ones. Our findings highlight the key role of histone acetylation in determining the 3D organization of chromatin domains, supporting the idea that the separation of active and inactive TADs in Drosophila, at least in part, is mediated by histone acetylation. These results may help to understand how agents such as histone deacetylase inhibitors exert their therapeutic effects in certain cancers and other human diseases.
SN - 1422-0067
ER -