 In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emer- gent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion. We show that packing domains are not topologically associated domains. Instead, packing domains exist across a structure- function life cycle that couples heterochromatin and transcription in situ, explaining how heterochromatin en- zyme inhibition can produce a paradoxical decrease in transcription by destabilizing domain cores. Applied to development and aging, we show the pairing of heterochromatin and transcription at myogenic genes that could be disrupted by nuclear swelling. In sum, packing domains represent a foundation to explore the interactions of chromatin and transcription at the single-cell level in human health.
for LaTeX users @article{LMAlmassalha2025-11,
author = {L. M. Almassalha and M. Carignano and E. P. Liwag and W. S. Li and R. Gong and N. Acosta and C. L. Dunton and P. C. Gonzalez and L. M. Carter and R. Kakkaramadam and M. Kr\"oger and P. Su and T. Kuo and K. I. Medina and J. A. Pritchard and A. Skol and R. Nap and M. Kanemaki and V. Dravid and I. Szleifer and V. Backman},
title = {Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system},
journal = {Sci. Adv.},
volume = {11},
pages = {eadq6652},
year = {2025},
doi = {10.1126/sciadv.adq6652}
}
\bibitem{LMAlmassalha2025-11} L.M. Almassalha, M. Carignano, E.P. Liwag, W.S. Li, R. Gong, N. Acosta, C.L. Dunton, P.C. Gonzalez, L.M. Carter, R. Kakkaramadam, M. Kr\"oger, P. Su, T. Kuo, K.I. Medina, J.A. Pritchard, A. Skol, R. Nap, M. Kanemaki, V. Dravid, I. Szleifer, V. Backman,
Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system,
Sci. Adv. {\bf 11} (2025) eadq6652.LMAlmassalha2025-11
L.M. Almassalha, M. Carignano, E.P. Liwag, W.S. Li, R. Gong, N. Acosta, C.L. Dunton, P.C. Gonzalez, L.M. Carter, R. Kakkaramadam, M. Kr\"oger, P. Su, T. Kuo, K.I. Medina, J.A. Pritchard, A. Skol, R. Nap, M. Kanemaki, V. Dravid, I. Szleifer, V. Backman
Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system
Sci. Adv.,11,2025,eadq6652 |
mk@mat.ethz.ch
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