A scaffolding element rewires local 3D chromatin architecture during differentiation
- 1Institute of Human Genetics, CNRS and University of Montpellier, Montpellier, France.
- 2Institute of Human Genetics, CNRS and University of Montpellier, Montpellier, France. [email protected].
Abstract
During differentiation chromatin and transcription are rewired to reflect the new cellular identity. However, what drives these changes and their mutual relationship remains unclear. Here, we use mouse ESC-to-NPC differentiation to study rewiring at a 3 Mb large Zfp608 locus. This large chromatin domain splits in half at the Zfp608 promoter, local chromatin gets littered with activating marks, compacts in 3D space and Zfp608 transcription is induced. We combine capture Hi-C (cHi-C), biophysical modelling, and 3-color 3D-FISH to investigate cis and trans elements driving this process. We find that transcription modulates both, local chromatin contacts and insulation at the domain split and we identify a genetic element with dual enhancer/architectural function essential for chromatin rewiring and loop formation, a scaffolding element. Together, these results demonstrate that a hierarchy of genetic elements in cis allows successful rewiring during differentiation and that multiple trans acting elements contribute to making this rewiring efficient.
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BibTeX
@article{jerkovic2026scaffolding,
title = {{A scaffolding element rewires local 3D chromatin architecture during differentiation}},
author = {Ivana Jerković and Marco Di Stefano and Hadrien Reboul and Michael F Szalay and Davide Normanno and Flora Paldi and Giorgio L Papadopoulos and Quentin Szabo and Frederic Bantignies and Giacomo Cavalli},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77603-z},
url = {https://hal.science/hal-05803512v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A scaffolding element rewires local 3D chromatin architecture during differentiation
AU - Ivana Jerković
AU - Marco Di Stefano
AU - Hadrien Reboul
AU - Michael F Szalay
AU - Davide Normanno
AU - Flora Paldi
AU - Giorgio L Papadopoulos
AU - Quentin Szabo
AU - Frederic Bantignies
AU - Giacomo Cavalli
PY - 2026
DA - 2026/09/15
JO - Nature Communications
DO - 10.1038/s41467-026-77603-z
UR - https://hal.science/hal-05803512v1
AB - During differentiation chromatin and transcription are rewired to reflect the new cellular identity. However, what drives these changes and their mutual relationship remains unclear. Here, we use mouse ESC-to-NPC differentiation to study rewiring at a 3 Mb large Zfp608 locus. This large chromatin domain splits in half at the Zfp608 promoter, local chromatin gets littered with activating marks, compacts in 3D space and Zfp608 transcription is induced. We combine capture Hi-C (cHi-C), biophysical modelling, and 3-color 3D-FISH to investigate cis and trans elements driving this process. We find that transcription modulates both, local chromatin contacts and insulation at the domain split and we identify a genetic element with dual enhancer/architectural function essential for chromatin rewiring and loop formation, a scaffolding element. Together, these results demonstrate that a hierarchy of genetic elements in cis allows successful rewiring during differentiation and that multiple trans acting elements contribute to making this rewiring efficient.
SN - 2041-1723
SN - 2041-1723
ER -