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Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE291992 | GEO | 2025/12/11

REPOSITORIES: GEO

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Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [RNA-Seq]

Project description:A remarkable transition during murine development is the progression from the 1-cell embryo to the 2-cell stage, accompanied by the activation of a specific set of embryonic genes, epigenome reprogramming, and nuclear architecture reorganization. Some of these characteristics are recapitulated in vitro with the spontaneous emergence of 2-cell-like cells from mouse embryonic stem cells, which exhibit a transcriptomic signature resembling the 2-cell stage, including the expression of genes such as Dux, Zscan4, and the repetitive element MERVL, and a more relaxed chromatin state. Here, we show that inter-and intra-chromosomal interactions, driven by Zscan4 chromatin factors, form during this transition and segregate into a distinct genomic compartment (Z compartment). Mechanistically, the formation of Z-DNA, an alternative DNA conformation regulated by polyamine levels, promotes the emergence of totipotent-like cells and the establishment of the Z compartment. This compartment is characterized by a decrease in active histone marks and a reduced expression of genes associated with differentiation and late developmental processes. Overall, these findings suggest that Z-DNA formation may play a dual role, first in activating ZGA genes and later in guiding genome compartmentalization to safeguard the totipotent-like state by restricting the expression of non-ZGA genes within a permissive chromatin environment.

2025-12-11 | GSE291987 | GEO

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [Hi-C]

2025-12-11 | GSE291983 | GEO

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [scRNA-seq]

2025-12-11 | GSE291990 | GEO

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [methyl-seq]

2025-12-11 | GSE291988 | GEO

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization

Project description:Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization

| PRJNA1236291 | ENA

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [Hi-C]

Project description:Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [Hi-C]

| PRJNA1236289 | ENA

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [scRNA-seq]

Project description:Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [scRNA-seq]

| PRJNA1236296 | ENA

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [RNA-Seq]

Project description:Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [RNA-Seq]

| PRJNA1236288 | ENA

Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [methyl-seq]

Project description:Z-DNA formation induces the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization [methyl-seq]

| PRJNA1236293 | ENA

Chromatin compartmentalization regulates the response to DNA damage.

Project description:The DNA damage response is essential to safeguard genome integrity. Although the contribution of chromatin in DNA repair has been investigated1,2, the contribution of chromosome folding to these processes remains unclear3. Here we report that, after the production of double-stranded breaks (DSBs) in mammalian cells, ATM drives the formation of a new chromatin compartment (D compartment) through the clustering of damaged topologically associating domains, decorated with γH2AX and 53BP1. This compartment forms by a mechanism that is consistent with polymer-polymer phase separation rather than liquid-liquid phase separation. The D compartment arises mostly in G1 phase, is independent of cohesin and is enhanced after pharmacological inhibition of DNA-dependent protein kinase (DNA-PK) or R-loop accumulation. Importantly, R-loop-enriched DNA-damage-responsive genes physically localize to the D compartment, and this contributes to their optimal activation, providing a function for DSB clustering in the DNA damage response. However, DSB-induced chromosome reorganization comes at the expense of an increased rate of translocations, also observed in cancer genomes. Overall, we characterize how DSB-induced compartmentalization orchestrates the DNA damage response and highlight the critical impact of chromosome architecture in genomic instability.

| S-EPMC10620078 | biostudies-literature

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