Amazing stuff! Better instruments, the closer you look, more discoveries!
Mitosis is still a mystery!
"... However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis. ...
In 2023, Hansen and others developed a new technique that allows them to analyze 3D genome structures with 100 to 1,000 times greater resolution than was previously possible.
This technique, known as Region-Capture Micro-C (RC-MC), uses a different enzyme that cuts the genome into small fragments of similar size. It also focuses on a smaller segment of the genome, allowing for high-resolution 3D mapping of a targeted genome region.
Using this technique, the researchers were able to identify a new kind of genome structure that hadn't been seen before, which they called "microcompartments." These are tiny highly connected loops that form when enhancers and promoters located near each other stick together. ...
"This study leverages the unprecedented genomic resolution of the RC-MC assay to reveal new and surprising aspects of mitotic chromatin organization, which we have overlooked in the past using traditional 3C-based assays. The authors reveal that, contrary to the well-described dramatic loss of TADs and compartmentalization during mitosis, fine-scale 'microcompartments'—nested interactions between active regulatory elements—are maintained or even transiently strengthened," ..."
From the abstract:
"As cells exit mitosis and enter G1, chromosomes decompact and transcription is reestablished. Hi-C studies have indicated that all interphase three-dimensional genome features, including A/B compartments, topologically associating domains and CCCTC-binding factor loops, are lost during mitosis.
However, Hi-C is insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements.
Here we apply region capture Micro-C to mouse erythroblasts from mitosis to G1. We unexpectedly observe microcompartments in prometaphase, which strengthen in anaphase and telophase before weakening throughout G1. Microcompartment anchors coincide with transcriptionally spiking promoters during mitosis. Loss of condensin loop extrusion differentially impacts microcompartments and A/B compartments, suggesting that they are partially distinct. Polymer modeling shows that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion, providing a basis for strong microcompartmentalization in anaphase and telophase. Our results suggest that compaction and homotypic affinity drive microcompartment formation, which may explain transient transcriptional spiking at mitotic exit."
Fig. 1: RCMC deeply resolves 3D genomic architecture at the M-to-G1 transition.
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