The epigenetic reader Phf2 is positioned in the genome by cohesin
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ABSTRACT:
PROVIDER: PRJNA1185173 | ENA |
REPOSITORIES: ENA
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Project description:Eukaryotic genomes are assembled into chromatin by histones and extruded into loops by cohesin. These mechanisms control important genomic functions, but whether histones and cohesin cooperate in genome regulation is poorly understood. Here we identify Phf2, a member of the Jumonji-C family of histone demethylases, as a cohesin-interacting protein. Phf2 binds to H3K4me3 nucleosomes at active transcription start sites (TSSs) but also co-localizes with cohesin. Cohesin depletion reduces Phf2 binding at sites lacking H3K4me3, and depletion of Wapl and CTCF re-positions Phf2 together with cohesin in the genome, resulting in the accumulation of both proteins in vermicelli and cohesin islands. Conversely, Phf2 depletion reduces cohesin binding at TSSs lacking CTCF, decreases the number of short cohesin loops, but increases the length of heterochromatic B compartments. These results suggest that Phf2 is an ‘epigenetic reader’, which is translocated through the genome by cohesin-mediated DNA loop extrusion, and which recruits cohesin to active TSSs and limits the size of B compartments. These findings reveal an unexpected degree of cooperativity between epigenetic and architectural mechanisms of eukaryotic genome regulation.
2024-12-18 | PXD057926 | Pride
Project description:Eukaryotic genomes are assembled into chromatin by histones and extruded into loops by cohesin. These mechanisms control important genomic functions, but whether histones and cohesin cooperate in genome regulation is poorly understood. Here we identify Phf2, a member of the Jumonji-C family of histone demethylases, as a cohesin-interacting protein. Phf2 binds to H3K4me3 nucleosomes at active transcription start sites (TSSs) but also co-localizes with cohesin. Cohesin depletion reduces Phf2 binding at sites lacking H3K4me3, and depletion of Wapl and CTCF re-positions Phf2 together with cohesin in the genome, resulting in the accumulation of both proteins in vermicelli and cohesin islands. Conversely, Phf2 depletion reduces cohesin binding at TSSs lacking CTCF, decreases the number of short cohesin loops, but increases the length of heterochromatic B compartments. These results suggest that Phf2 is an ‘epigenetic reader’, which is translocated through the genome by cohesin-mediated DNA loop extrusion, and which recruits cohesin to active TSSs and limits the size of B compartments. These findings reveal an unexpected degree of cooperativity between epigenetic and architectural mechanisms of eukaryotic genome regulation.
2024-12-19 | GSE281657 | GEO
Project description:Eukaryotic genomes are assembled into chromatin by histones and extruded into loops by cohesin. These mechanisms control important genomic functions, but whether histones and cohesin cooperate in genome regulation is poorly understood. Here we identify Phf2, a member of the Jumonji-C family of histone demethylases, as a cohesin-interacting protein. Phf2 binds to H3K4me3 nucleosomes at active transcription start sites (TSSs) but also co-localizes with cohesin. Cohesin depletion reduces Phf2 binding at sites lacking H3K4me3, and depletion of Wapl and CTCF re-positions Phf2 together with cohesin in the genome, resulting in the accumulation of both proteins in vermicelli and cohesin islands. Conversely, Phf2 depletion reduces cohesin binding at TSSs lacking CTCF, decreases the number of short cohesin loops, but increases the length of heterochromatic B compartments. These results suggest that Phf2 is an ‘epigenetic reader’, which is translocated through the genome by cohesin-mediated DNA loop extrusion, and which recruits cohesin to active TSSs and limits the size of B compartments. These findings reveal an unexpected degree of cooperativity between epigenetic and architectural mechanisms of eukaryotic genome regulation.
2024-12-19 | GSE278143 | GEO
Project description:Eukaryotic genomes are assembled into chromatin by histones and extruded into loops by cohesin. These mechanisms control important genomic functions, but whether histones and cohesin cooperate in genome regulation is poorly understood. Here we identify Phf2, a member of the Jumonji-C family of histone demethylases, as a cohesin-interacting protein. Phf2 binds to H3K4me3 nucleosomes at active transcription start sites (TSSs) but also co-localizes with cohesin. Cohesin depletion reduces Phf2 binding at sites lacking H3K4me3, and depletion of Wapl and CTCF re-positions Phf2 together with cohesin in the genome, resulting in the accumulation of both proteins in vermicelli and cohesin islands. Conversely, Phf2 depletion reduces cohesin binding at TSSs lacking CTCF, decreases the number of short cohesin loops, but increases the length of heterochromatic B compartments. These results suggest that Phf2 is an ‘epigenetic reader’, which is translocated through the genome by cohesin-mediated DNA loop extrusion, and which recruits cohesin to active TSSs and limits the size of B compartments. These findings reveal an unexpected degree of cooperativity between epigenetic and architectural mechanisms of eukaryotic genome regulation.
2024-12-20 | GSE278142 | GEO
Project description:The epigenetic reader Phf2 is positioned in the genome by cohesin [HiC]
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Project description:The epigenetic reader Phf2 is positioned in the genome by cohesin [ChIP-seq]
| PRJNA1165761 | ENA
Project description: Not available
| S-BSST1714 | biostudies-other
Project description:Important hallmark of neurogenesis is activation of quiescent neural stem cells (NSC) in dentate gyrus. Precise mechanisms of NSC activation are not fully clear. In the current study we interrogate the role of homeodomain finger protein 2 (Phf2) in this process. Here we performed mouse transcriptome RNA-seq profiling of epigenetic regulator Phf2 in neural stem cells without and with knock-down in order to uncover mechanistic components/pathways affecting protein translational capacity in activated NSC.
2023-05-30 | GSE159311 | GEO
Project description:The activation of quiescent neural stem cells (qNSCs) in the dentate gyrus is required for lifelong neurogenesis. However, the mechanisms that promote the exit of neural stem cells (NSCs) from quiescence remain elusive. We demonstrate that the expression of plant homeodomain finger protein 2 (Phf2) activates the exit of postnatal mouse NSC from shallow quiescence. Loss of Phf2 prevents NSC activation and neurogenesis in postnatal 30 (P30) mice but does not decrease the label-retaining NSC pool, indicating that Phf2 is not required for the exit of NSC from quiescence. NSC-specific deletion of Phf2 modestly compromises embryonic mouse NSC proliferation without increasing apoptosis, indicating that Phf2 is crucial for embryonic development. Moreover, human cortical organoids reveal that Phf2 promotes NPC proliferation via a lysine demethylase-independent manner. Mechanistically, Phf2 directly binds to the cohesion complex via Rad21 and regulates the DNA replication in mouse NSC by associating with the cohesion complex releasing protein Wapl activity. Our study identifies the Phf2-cohesin complex mediated DNA replication for neural stem cell activation in a lysine demethylase-independent manner.
2024-03-01 | PXD040515 | JPOST Repository
Project description:CTCF binding sites serve as anchors for the 3D chromatin architecture in vertebrates. The functionality of these anchors is influenced by the residence time of CTCF on chromatin, which is determined by its binding affinity and its interactions with nucleosomes and other chromatin-associated factors. In this study, we demonstrate that CTCF occupancy is driven by CTCF motifs strategically positioned at the entry sites of well-positioned nucleosome, such that, upon binding, the N-terminus of CTCF is oriented towards the nucleosome. We refer to this nucleosome as the CTCF priming nucleosome (CpN). CTCF recognizes its binding sites as long as they are not methylated. It can then displace the CpN, provided the nucleosome is not marked by CpG methylation or repressive histone modifications. Under these permissive conditions, the N-terminus of CTCF recruits SMARCA5 to reposition the CpN downstream, thereby creating nucleosome-free regions that enhance CTCF occupancy and cohesin stalling. In contrast, when CpNs carry repressive epigenetic marks, CTCF binding is transient, without nucleosome displacement or chromatin opening. In such cases, cohesin is not effectively retained at CTCF binding sites. We propose that the epigenetic status of CpNs governs cell-specific CTCF binding patterns, ensuring the maintenance of chromatin architecture throughout the cell cycle.
2024-09-24 | GSE277826 | GEO