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Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L

ABSTRACT: Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L

PROVIDER: PRJNA925865 | ENA |

REPOSITORIES: ENA

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Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [RNA-seq]

Project description:The histone methyltransferase DOT1L catalyzes methylation of H3K79 and it is highly conserved in mammals. DOT1L plays a functional role in several biological processes including cell cycle regulation, DNA repair, RNA splicing and gene expression, suggesting a complex role in chromatin organization and regulation. Such a remarkable range of functions performed by DOT1L can be the result, at least partially, of its interaction with a plethora of proteins and presence in different complexes. Here, we characterized the cooperation of DOT1L with the nucleolar protein NPM1 and the impact of both proteins on peri-nucleolar heterochromatin activity. We show that i) DOT1L interacts preferentially with monomeric NPM1 in the nucleus; ii) DOT1L acts in concert with NPM1 to maintain each other’s protein homeostasis; iii) NPM1 depletion results in H3K79me2 upregulation at chromatin remodeling genes and transcriptional activation of Ezh2; iv) DOT1L and NPM1 preserved DNA satellite expression at peri-nucleolar heterochromatin via epigenetic mechanisms dependent on H3K27me3. Our findings give insights into molecular mechanisms employed by DOT1L and NPM1 to regulate heterochromatin activities around the nucleoli and shed light on one aspect of the complex role of both proteins in chromatin dynamics.

2024-01-01 | GSE223362 | GEO

Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [ChIP-seq]

Project description:The histone methyltransferase DOT1L catalyzes methylation of H3K79 and it is highly conserved in mammals. DOT1L plays a functional role in several biological processes including cell cycle regulation, DNA repair, RNA splicing and gene expression, suggesting a complex role in chromatin organization and regulation. Such a remarkable range of functions performed by DOT1l can be the result, at least partially, of its interaction with different proteins and presence in different complexes. Here, we characterized the interaction of DOT1L with the nucleolar protein NPM1 and the impact of the DOT1L/NPM1 complex on nucleoli organization and activity. We show that i) DOT1L interacts preferentially with monomeric NPM1 in the nucleus; ii) DOT1L interaction with NPM1 is key to maintain their protein homeostasis; iii) NPM1 depletion results in H3K79me2 upregulation at chromatin remodeling genes; iv) DOT1L/NPM1 complex preserved peri-nucleolar heterochromatin organization via epigenetic mechanisms. Our findings unravel the molecular mechanisms employed by the DOT1L/NPM1 complex to maintain heterochromatin organization around the nucleoli and shed light on one aspect of the complex role of DOT1L in chromatin dynamics.

2024-01-01 | GSE223361 | GEO

Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [ChIP-seq]

Project description:Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [ChIP-seq]

| PRJNA925871 | ENA

Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [RNA-seq]

Project description:Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L [RNA-seq]

| PRJNA925870 | ENA

Nucleophosmin 1 regulates H3K79me2 levels and peri-nucleolar heterochromatin organization through interaction with the methyltransferase DOT1L

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-01 | GSE223363 | GEO

DOT1L-mediated Murine Neuronal Differentiation associates with H3K79me2 Accumulation and preserves SOX2-Enhancer Accessibility

Project description:To study whether acute inhibition of DOT1L induces global chromatin states alterations, we profile and compare the transcriptome, chromatin accessibility and epigenome (H3K4me3, H3K4me1, H3K27ac, H3K27me3, H3K36me3, H3K9me3, H3K79me2) of mESC and ES-derived NPC, treated with DMSO or EPZ5676.

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H3K79me2 naïve and in vitro activated B cells

Project description:We studied the role of the histone methyltransferase DOT1L in B cell development and differentiation. H3K79me2 ChIP-sequencing data was generated from sorted B cells. This was compared to RNA-sequencing data from WT and Dot1L KO mice in order to study the link between H3K79me2 and transcription.

2020-11-19 | GSE138906 | GEO

Assesment of DOT1L direct targets via ChIP of H3K79me2 at E12.5 of mouse cortex

Project description:Cortical development is under control of transcriptional programs that are orchestrated by activation of key determinants such as transcription factors. But stable inheritance of temporo-spatial activity of factors influencing cell fate and regionalization in different layers is only partly understood. We report that chromatin methylation at H3K79 transmits cell fate and layering information from early to late progenitors. Activity of DOT1L, mediating H3K79 methylation, prevents premature cell cycle exit by increasing expression of genes regulating asymmetric cell division (Vangl2, Cenpj). Transcriptional programs characteristic for upper layer neurons are less active in Dot1l-deficient mice already at developmental stages that precede upper layer neuron generation. DOT1L activates expression of many key determinants such as Cux1, Cux2, Satb2 or Pou3f3. Additionally, DOT1L affects transcription of Sox family members, suggesting an evolutionary conserved mechanism. In part, DOT1L and H3K79me2 replace inactivating H3K9me3 at Sox family promoters and allow for transcriptional activation during neural differentiation.

2017-12-31 | GSE95831 | GEO

Expression profiling of WT and Dot1L KO CD8 effector T cells and H3K79me2 occupancy in WT effector CD8 T cells

Project description:We studied the role of the histone methyltransferase DOT1L in T cell development and differentiation. We generated RNA-seq data from sorted CD8 effector T cells from WT (Lck-cre+/-) and Dot1L KO (Lck-cre+/-;Dot1Lfl/fl) mice infected with Listeria monocytogenes. This data was compared with H3K79me2 ChIP-seq data from the same T cell subset.

2021-08-01 | GSE155406 | GEO

H3K79me2 and H3K4me3 in CD8 T cell subsets

Project description:We studied the role of the histone methyltransferase DOT1L in T cell development and differentiation. H3K79me2 and H3K4me3 ChIP-sequencing data was generated from sorted CD8 single positive thymocytes, naïve CD8 splenocytes and memory CD8 splenocytes. This was compared to RNA-sequencing data from WT and Dot1L KO mice in order to study the link between H3K79me2 and transcription.

2020-07-29 | GSE138908 | GEO

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