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DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

ABSTRACT: The role of G-quadruplex (G4) structures and their effects on oocyte and early embryo development remain unclear. We discovered that the G4 helicase DHX36 is essential for oocyte growth and the maternal-to-zygotic transition (MZT). Conditional knockout of DHX36 resulted in DNA G4 accumulation in mouse oocytes, reducing chromatin accessibility, and inhibiting RNA transcription, ultimately disrupting transcriptome homeostasis during oocyte growth and MZT.

ORGANISM(S): Mus musculus

PROVIDER: GSE266915 | GEO | 2025/01/29

REPOSITORIES: GEO

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DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:The role of G-quadruplex (G4) structures and their effects on meiosis resumption and early embryo development remain unclear. We discovered that the G4 helicase DHX36 is essential for oocyte growth and the maternal-to-zygotic transition (MZT). Conditional knockout of DHX36 resulted in DNA G4 accumulation in mouse oocytes, reducing chromatin accessibility, and inhibiting RNA transcription, ultimately disrupting transcriptome homeostasis during oocyte growth and MZT.

2025-01-29 | GSE266885 | GEO

Rapid degradation of DHX36 revealing its transcriptional role by interacting with G-quadruplex

Project description:More evident supports G-quadruplex are involved in transcription. Recent research revealed that DHX36 preferentially resolves G-quadruplex (G4) structure over the canonical G4, raising the possibility that DHX36 could bind and resolve G4 structures to regulate gene transcription. However, the hypothesis has yet been validated systematically in vivo.In this study, we investigated the role of DHX36 interacting with G4s in transcription. Firstly, we performed CUT&TAG to map the binding sites in chromatin of MCF7. Next, we utilized nascent RNA-seq and AID protein degradation system to identify the direct gene targets by transcriptional regulation of DHX36 and found these sites are enriched with G4 structure. We picked three G4 sequences in oncogene from these sites and found DHX36 binds and resolves these G4 structures in vitro, suggesting DHX36 may be recruited to these promoter G4 sites and regulate gene transcription by resolving G4 structure.

2024-08-13 | GSE228815 | GEO

DNA/RNA helicase DHX36 is required for late stages of spermatogenesis

Project description:Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, play crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we delete Dhx36 in advanced germ cells with Stra8-GFPCre, and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 play crucial roles in the late stages of spermatogenesis.

2022-11-24 | GSE218477 | GEO

DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

| PRJNA1108710 | ENA

DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

Project description:DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

| PRJNA1108676 | ENA

RNA-seq comparing the WT mouse hearts versus Dhx36 cKO hearts

Project description:This experiment aimed to investigate the transcriptional role of G4 resolvase Dhx36 in the adult mouse heart. We compared three pools of wild-type (WT) mouse hearts with three pools of Dhx36 conditional knockout (cKO) hearts. In the mutant mice, Dhx36 was conditionally deleted in cardiomyocytes using the Myh6-cre transgenic line. Each of the six pools was created using RNA extracted from 3-5 hearts from mice aged approximately 21 days. The cKO mice developed dilated cardiomyopathy and began experiencing sudden death at 40 days old, with no mutants surviving beyond 5 months.

2024-09-15 | E-MTAB-14440 | biostudies-arrayexpress

Single nuclei RNA-seq and snATAC-seq multiome performed in WT and Dhx36 conditional KO hearts at postnatal day 7 (PD7)

Project description:In these experiments, we aimed to investigate the role of cardiomyocyte-specific deletion of the G-quadruplex resolvase Dhx36 in heart development and cardiomyocyte differentiation. To achieve this, we conducted multi-omics analysis using single-nuclei RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) on hearts from postnatal day 7 (PD7) wild-type (WT) and Dhx36 conditional knockout (cKO) mice. Our findings reveal that Dhx36 plays a critical role in the development of the cardiac conduction system (CCS) and in the differentiation of both CCS and working cardiomyocytes

2024-09-15 | E-MTAB-14441 | biostudies-arrayexpress

Single nuclei RNA-seq and snATAC-seq multiome performed in WT and Dhx36 conditional KO hearts at postnatal day 7 (PD7)

2024-09-15 | E-MTAB-14442 | biostudies-arrayexpress

Multistep mechanism of G-quadruplex resolution during DNA replication

Project description:G-quadruplex (or G4) structures are non-canonical DNA structures that form in guanine-rich sequences and threaten genome stability when not properly resolved. G4 unwinding occurs during S phase via an unknown mechanism. Using Xenopus egg extracts, we define a three-step G4 unwinding mechanism that acts during DNA replication. First, the replicative helicase (CMG) stalls at a leading strand G4 structure. Second, the DHX36 helicase mediates the bypass of the CMG past the intact G4 structure, which allows approach of the leading strand to the G4. Third, G4 structure unwinding by the FANCJ helicase enables the DNA polymerase to synthesize past the G4 motif. A G4 on the lagging strand template does not stall CMG, but still requires active DNA replication for unwinding. DHX36 and FANCJ have partially redundant roles, conferring robustness to this pathway. Our data reveal a novel genome maintenance pathway that promotes faithful G4 replication thereby avoiding genome instability.

2022-02-17 | PXD027623 | Pride

SMaRT lncRNA controls translation of a G-quadruplex containing mRNA antagonizing the DHX36 helicase

Project description:Guanine-quadruplexes (G4) present in RNA and DNA exert a number of different functions in the nucleus and in the cytoplasm. However, the molecular mechanisms of G4-mediated regulation are still poorly understood. We describe a regulatory circuitry operating in the early phases of muscle differentiation in which a long non coding RNA (SMaRT) base pairs with a G4-containing mRNA (Mlx-g) and represses its translation in an antagonistic way with the RNA helicase DHX36. MLX-g is required to allow the nuclear translocation of the MLX-a and b dimerization partners and to control proper myogenesis. We show that by controlling MLX-g, lnc-SMaRT is able to regulate the overall quantity of nuclear MLX proteins and their transcriptional output. Therefore, the circuitry composed by lnc-SMaRT, Mlx-g and Dhx36 not only plays an important role in the control of myogenesis but unravels a molecular mechanism where G4 structures and G4 unwinding activities are controlled in vivo.

2020-03-18 | GSE128486 | GEO

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