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复制解旋酶 CMG 在体内不对称细胞分裂过程中细胞命运分歧是必需的。

The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo.

机构信息

Research Department Cell and Developmental Biology, Division of Biosciences, University College London, London, UK.

Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, South Korea.

出版信息

Nat Commun. 2024 Oct 30;15(1):9399. doi: 10.1038/s41467-024-53715-2.

DOI:10.1038/s41467-024-53715-2
PMID:39477966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11525967/
Abstract

We report that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for differential gene expression in cells produced by asymmetric cell divisions in C. elegans. We found that the C. elegans CMG component, PSF-2 GINS2, is necessary for transcriptional upregulation of the pro-apoptotic gene egl-1 BH3-only that occurs in cells programmed to die after they are produced through asymmetric cell divisions. We propose that CMG's histone chaperone activity causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for egl-1 upregulation in cells programmed to die. We find that PSF-2 is also required for the divergence of other cell fates during C. elegans development, suggesting that this function is not unique to egl-1 expression. Our work uncovers an unexpected role of CMG in cell fate decisions and an intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.

摘要

我们报告称，真核复制解旋酶 CMG（Cdc45-MCM-GINS）在秀丽隐杆线虫通过不对称细胞分裂产生的细胞中差异基因表达是必需的。我们发现，秀丽隐杆线虫 CMG 成分 PSF-2 GINS2 对于凋亡基因 egl-1 BH3-only 的转录上调是必需的，该基因在通过不对称细胞分裂产生后被编程死亡的细胞中发生。我们提出，CMG 的组蛋白伴侣活性在母细胞复制过程中引起 egl-1 基因座的表观遗传变化，并且这些变化是编程死亡细胞中 egl-1 上调所必需的。我们发现 PSF-2 对于秀丽隐杆线虫发育过程中其他细胞命运的分化也是必需的，这表明该功能不是 egl-1 表达所特有的。我们的工作揭示了 CMG 在细胞命运决定中的一个意外作用，以及在不对称细胞分裂背景下基因表达可塑性的内在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/267c7f5ad715/41467_2024_53715_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/adc14546ac57/41467_2024_53715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/4712f60f326b/41467_2024_53715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/d24cfe7bb7dd/41467_2024_53715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/bd96bceabb39/41467_2024_53715_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/267c7f5ad715/41467_2024_53715_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/adc14546ac57/41467_2024_53715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/4712f60f326b/41467_2024_53715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/d24cfe7bb7dd/41467_2024_53715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/bd96bceabb39/41467_2024_53715_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc79/11525967/267c7f5ad715/41467_2024_53715_Fig5_HTML.jpg

相似文献

[1]
The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo.

Nat Commun. 2024-10-30

[2]
Caspase Is Required for Asymmetric Divisions That Generate Cells Programmed To Die.

Genetics. 2018-9-7

[3]
DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in .

Science. 2023-9-22

[4]
NMY-2, TOE-2 and PIG-1 regulate Caenorhabditis elegans asymmetric cell divisions.

PLoS One. 2024

[5]
Size Matters: How C. elegans Asymmetric Divisions Regulate Apoptosis.

Results Probl Cell Differ. 2017

[6]
Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS.

Curr Biol. 2012-1-26

[7]
The CMG (CDC45/RecJ, MCM, GINS) complex is a conserved component of the DNA replication system in all archaea and eukaryotes.

Biol Direct. 2012-2-13

[8]
The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair.

Cell. 2018-12-27

[9]
Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors -- apparent direct targets of the LIN-39 Hox protein.

Development. 2002-11

[10]
RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans.

G3 (Bethesda). 2016-10-13

引用本文的文献

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Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.

bioRxiv. 2025-5-12

本文引用的文献

[1]
WormBase 2024: status and transitioning to Alliance infrastructure.

Genetics. 2024-5-7

[2]
Asymmetric distribution of parental H3K9me3 in S phase silences L1 elements.

Nature. 2023-11

[3]
Mechanisms of lineage specification in Caenorhabditis elegans.

Genetics. 2023-12-6

[4]
Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation.

Nat Genet. 2023-9

[5]
Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity.

Nat Genet. 2023-9

[6]
A fork in the road to differentiation.

Nat Genet. 2023-9

[7]
Old and newly synthesized histones are asymmetrically distributed in Drosophila intestinal stem cell divisions.

EMBO Rep. 2023-7-5

[8]
The CMG DNA helicase and the core replisome.

Curr Opin Struct Biol. 2023-8

[9]
Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.

J Clin Immunol. 2023-7

[10]
labeling of endogenous genomic loci in using CRISPR/dCas9.

MicroPubl Biol. 2022-12-13

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