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 if these form a cohesive framework that regulates RNA transcription. Herein we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally-defined heterogenous, 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 transc..., The data was collected across a range of techniques including chromatin scanning transmission electron microscopy (ChromSTEM), multiplexed single molecule localization microscopy (SMLM), partial wave spectroscopic (PWS) microscopy), Hi-C, and ChIP-Seq. Details of the collection and analysis are within the materials and methods of the manuscript for each method., , # Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system

[https://doi.org/10.5061/dryad.b8gtht7p0](https://doi.org/10.5061/dryad.b8gtht7p0)

## Description of the data and file structure

Below is a brief summary of the included data:

Acronyms ActD refers to Actinomycin D, RAD21 refers to the cohesin protein 'RAD21', GSK refers to the EZH2 inhibitor GSK343, and TSA refers to the histone deacetylase inhibitor, trichostatin A. Unless otherwise specified, RNA Polymerase II in the single molecule localization microscopy images refers to Serine-2 phosphorylated protein state.

All of the .tif and .jpg files can be accessed with freely available ImageJ or FIJI software packages. .xlsx files can be opened with Excel.

### Figure 1.zip)

Image files of chromatin electron microscopy tomograms (images) from cells are included:

**A549.tif** represents the chromatin electron microscopy tomogram of an A549 cell
**BJ.tif** represents the tomogram of a BJ fibrob...