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This content will become publicly available on January 10, 2026

Title: Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system
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 emergent, 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 enzyme 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.  more » « less
Award ID(s):
1830961
PAR ID:
10596442
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; ; ; ; « less
Publisher / Repository:
AAAS
Date Published:
Journal Name:
Science Advances
Volume:
11
Issue:
2
ISSN:
2375-2548
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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