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β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner

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

ORGANISM(S): Mus musculus

PROVIDER: GSE235821 | GEO | 2024/02/29

REPOSITORIES: GEO

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β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [ATAC-Seq]

Project description:Replication stress is a main driver of functional decline of hematopoietic stem cells (HSCs), which carry the highest burden of maintaining genomic integrity and functionality within the hematopoietic system. Here, we identify a novel signaling axis in which β-catenin and Hoxa9 function in a compensatory manner to preserve HSC functionality by protecting DNA replication dynamics and genomic integrity, in part via regulation of Prmt1 activity. Co-inactivation of β-catenin and Hoxa9 induces severe hematopoietic defects accompanied by accumulating replication stress and DNA damage resulting in functional HSC decline. Furthermore, we illustrate how β-catenin and Hoxa9 pathways converge on the pivotal downstream target, Prmt1, which functions to maintain an adequate supply of DNA replication and repair factors. Prmt1 aids in alleviating replication stress and DNA damage accumulation thereby preserving HSC integrity and functionality.

2024-02-29 | GSE235815 | GEO

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [CUT&RUN]

2024-02-29 | GSE249199 | GEO

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq dKO_HSPCs]

2024-02-29 | GSE235817 | GEO

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq LSK]

2024-02-29 | GSE235816 | GEO

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner

Project description:β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner

| PRJNA987671 | ENA

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [CUT&RUN]

Project description:β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [CUT&RUN]

| PRJNA1047656 | ENA

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [ATAC-Seq]

Project description:β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [ATAC-Seq]

| PRJNA987675 | ENA

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq dKO_HSPCs]

Project description:β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq dKO_HSPCs]

| PRJNA987677 | ENA

β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq LSK]

Project description:β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [RNA-seq LSK]

| PRJNA987676 | ENA

Transcription shapes DNA replication initiation to preserve genome integrity.

Project description:BackgroundEarly DNA replication occurs within actively transcribed chromatin compartments in mammalian cells, raising the immediate question of how early DNA replication coordinates with transcription to avoid collisions and DNA damage.ResultsWe develop a high-throughput nucleoside analog incorporation sequencing assay and identify thousands of early replication initiation zones in both mouse and human cells. The identified early replication initiation zones fall in open chromatin compartments and are mutually exclusive with transcription elongation. Of note, early replication initiation zones are mainly located in non-transcribed regions adjacent to transcribed regions. Mechanistically, we find that RNA polymerase II actively redistributes the chromatin-bound mini-chromosome maintenance complex (MCM), but not the origin recognition complex (ORC), to actively restrict early DNA replication initiation outside of transcribed regions. In support of this finding, we detect apparent MCM accumulation and DNA replication initiation in transcribed regions due to anchoring of nuclease-dead Cas9 at transcribed genes, which stalls RNA polymerase II. Finally, we find that the orchestration of early DNA replication initiation by transcription efficiently prevents gross DNA damage.ConclusionRNA polymerase II redistributes MCM complexes, but not the ORC, to prevent early DNA replication from initiating within transcribed regions. This RNA polymerase II-driven MCM redistribution spatially separates transcription and early DNA replication events and avoids the transcription-replication initiation collision, thereby providing a critical regulatory mechanism to preserve genome stability.

| S-EPMC8188667 | biostudies-literature

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