The Chd4 chromatin remodeller controls temporal programs during retinal neurogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1105560 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR28824001_1.fastq.gz | Fastqsanger.gz | |||
| SRR28824001_2.fastq.gz | Fastqsanger.gz | |||
| SRR28824006_1.fastq.gz | Fastqsanger.gz | |||
| SRR28824006_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 25 |
Similar Datasets
Project description:During retinal development, neurons and glia are produced in a highly stereotyped and evolutionarily conserved birth order. Landmark studies have demonstrated that the sequence of cell production is temporally encoded. Transcription factors and heterochromatic determinants have been elsewhere implicated in the temporal regulation of progenitor competence states, but the underlying mechanisms are not well understood. Since chromatin remodelling complexes interact with both transcription factors and heterochromatic complexes such as polycomb, we focused on the nucleosome remodeller Chd4. We generated conditional knockouts (cKOs) of Chd4 – a key chromatin remodelling enzyme in neural progenitors. Chd4 cKOs exhibited a marked expansion in early-born retinal ganglion cells. Postnatally, rod photoreceptors were drastically underproduced. As a result, progenitors failed to be exhausted during late phases of development, leading to a striking increase in the production of Müller glia. Clonal retroviral lineaging and histological marker analyses suggest that these effects were independent of alterations in cell death or proliferation. Next, we examined the effect of Chd4 on the genome and transcriptome, focusing on retinal progenitors at P0/P1. Multi-seq single-cell transcriptomics demonstrated that deletion of Chd4 created divergent gene expression profiles and developmental trajectories. ATAC-seq experiments performed on sorted P1 retinal progenitors revealed that chromatin accessibility was significantly increased at ~10 000 enhancer elements and ~4000 genes in the Chd4 cKO, demonstrating that Chd4 is required to repress gene expression and genome accessibility. Finally, to determine whether Chd4 regulates retinal cell-type production by altering competence windows, we performed EdU birthdating. These experiments revealed that cell fates were altered without affecting competence windows. Thus, despite a very strong shift in the production of early-born and late-born cell types, our data suggest that chromatin remodelling does not directly regulate competence windows.
2025-05-31 | GSE266039 | GEO
Project description:During development, neural progenitor cells modify their output over time to produce different types of neurons and glia in chronological sequences. Previous studies have shown that epigenetic processes play a crucial role in regulating neural progenitor potential, but the underlying mechanisms are not well understood. Here, we hypothesized that nucleosome remodelling would regulate the competence transitions of retinal progenitors. We generated retina-specific conditional knockouts (cKOs) in the key nucleosome remodelling enzyme Chd4. Chd4 cKOs overproduced early-born retinal ganglion and amacrine cells. Postnatally, later-born rod photoreceptors were drastically underproduced. Concomitantly, progenitors failed to be exhausted at late phases of development and ultimately overproduced Müller glia. To determine how Chd4 regulates the genome, we used cut&run-seq to reveal Chd4 genome occupancy, and ATAC-seq experiments to visualize nucleosome remodelling. These data revealed that genome accessibility was significantly increased at ∼10,000 regulatory elements and ∼4,000 genes in the Chd4 cKO. Together, these results suggest that Chd4 restricts the genome to repress progenitor identity and promote rod photoreceptor production. Accordingly, multiplexed single-cell transcriptomics demonstrated that deletion of Chd4 led to markedly divergent gene expression profiles. However, despite overproduction of early fates and underproduction of later-born rods, the perinatal transition between early and late progenitor competence was not altered as determined by birthdating experiments and transcriptomic signatures. Taken together, our data suggest that Chd4-dependent chromatin remodelling regulates cell fate specification, and is also required to terminate retinal neurogenesis, but that it does not regulate the progenitor competence windows that restrict early-vs. late-cell-type production.
2025-09-02 | GSE300175 | GEO
Project description:This study investigates the role of the chromatin remodeller CHD4 in regulating gene expression. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. RNA-seq was performed at multiple time-points (1, 2, 4 and 24 hours) following auxin treatment to capture changes in gene expression upon CHD4 depletion. For each time point, three biological replicates were processed. This dataset aims to characterise the immediate effects of CHD4 loss on gene expression.
2026-01-15 | E-MTAB-15102 | biostudies-arrayexpress
Project description:This study investigates the role of the chromatin remodeller CHD4 in regulating gene expression. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. RNA-seq of nascent transcripts was performed at multiple time-points (1, 2, 4 and 24 hours) following auxin treatment to capture changes in gene expression upon CHD4 depletion. For each time point, three biological replicates were processed. This dataset aims to characterise the immediate effects of CHD4 loss on gene expression.
2026-01-15 | E-MTAB-15127 | biostudies-arrayexpress
Project description:This study investigates the role of the chromatin remodeller CHD4 in regulating chromatin accessibility. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. ATAC-seq was performed at multiple time-points (30 minutes, 1 hour, and 4 hours) following auxin treatment to capture changes in chromatin accessibility upon CHD4 depletion. For each time point, two biological replicates were processed, each with two technical replicates. This dataset aims to characterise the immediate effects of CHD4 loss on chromatin accessibility.
2026-01-15 | E-MTAB-15037 | biostudies-arrayexpress
Project description:This study investigates the effect of the chromatin remodeller CHD4 on MBD3 using CUT&Tag. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. CUT&Tag for MBD3 was performed at multiple time-points (4 hours and 24 hours) following auxin treatment vs untreated control (0 hours) to capture changes in MBD3 binding upon CHD4 depletion. For each time point, two biological replicates were processed.
2026-01-15 | E-MTAB-15627 | biostudies-arrayexpress
Project description:This study investigates the effect of the chromatin remodeller CHD4 on H3K27Ac and H3K4Me1 using CUT&Tag. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. CUT&Tag for H3K27Ac and H3K4Me1 was performed at multiple time-points (4 hours and 24 hours) following auxin treatment vs untreated control (0 hours) to capture changes in histone modifications upon CHD4 depletion. For each time point, three biological replicates were processed.
2026-01-15 | E-MTAB-15625 | biostudies-arrayexpress
Project description:This study investigates the role of the chromatin remodeller CHD4 in regulating transcription factor binging using CUT&RUN. CHD4 was tagged with a mini-AID degron to enable auxin-inducible degradation. CUT&RUN for Nanog and Sox2 was performed at multiple time-points (30 minutes, 1 hour, and 4 hours) following auxin treatment to capture changes in their binding upon CHD4 depletion. For each time point, two biological replicates were processed, each with two technical replicates. This dataset aims to characterise the immediate effects of CHD4 loss on TF binding.
2026-01-15 | E-MTAB-15607 | biostudies-arrayexpress
Project description:How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.
2016-01-26 | GSE64781 | GEO
Project description:The vertebrate retina serves as a model for studying neurogenesis and cell fate specification, with retinal progenitor cells following a tightly regulated temporal sequence to generate distinct cell types. Meis1 and Meis2 are transcription factors implicated in early retinal development, but their role in late-stage RPCs remains poorly understood. Here, we investigate whether Meis1 and Meis2 overexpression in postnatal mouse RPCs can alter temporal identity and induce early-born cell types. Using electroporation and single-cell RNA sequencing, we find that while these factors modestly upregulate early-stage gene regulatory network components, they do not repress late-stage transcription factors or induce early-born retinal cells. Meis1 overexpression reduces proliferation and inhibits neurogenesis, whereas Meis2 overexpression accelerates neurogenic progression without altering fate commitment. Our findings suggest that overexpression of Meis1 and Meis2 modulate largely non-overlapping aspects of temporal identity and neurogenic competence but are insufficient to fully reprogram late-stage progenitors. These results have implications for regenerative strategies aimed at reprogramming retinal cells for therapeutic purposes.
2025-10-07 | GSE295688 | GEO