Dynamics of microcompartment formation at the mitosis-to-G1 transition
Viraat Y. Goel, Nicholas G. Aboreden, James M. Jusuf, Haoyue Zhang, Luisa P. Mori, Leonid A. Mirny, Gerd A. Blobel, Edward J. Banigan, Anders S. Hansen
bioRxiv 2024.09.16.611917; doi: https://doi.org/10.1101/2024.09.16.611917
This article is a preprint and has not been certified by peer review
Abstract
As cells exit mitosis and enter G1, mitotic chromosomes decompact and transcription is reestablished. Previously, Hi-C studies showed that essentially all interphase 3D genome features including A/B-compartments, TADs, and CTCF loops, are lost during mitosis. However, Hi-C remains insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements (CREs). We therefore applied Region Capture Micro-C to cells from mitosis to G1. Unexpectedly, we observe microcompartments in prometaphase, which further strengthen in ana/telophase before gradually weakening in G1. Loss of loop extrusion through condensin depletion differentially impacts microcompartments and large A/B-compartments, suggesting that they are partially distinct. Using polymer modeling, we show that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion activity, explaining why ana/telophase likely provides a particularly favorable environment. Our results suggest that CREs exhibit intrinsic homotypic affinity leading to microcompartment formation, which may explain transient transcriptional spiking observed upon mitotic exit.