INO80 promotes and safeguards bivalency [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE158544 | GEO | 2021/07/04
REPOSITORIES: GEO
Similar Datasets
Project description:INO80 is involved in many chromatin-dependent functions. However, its role in pluripotency has not been fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the primed state. Mechanistically, INO80 co-occupied gene promoters that were bivalently marked by H3K4me3 and H3K27me3. Further, its occupancy was required for H3K27me3 installation and maintenance, as well as downstream gene repression. Finally, INO80 promoted H2A.Z occupancy at the bivalent domains, which in turn facilitated the polycomb repressive complex 2 (PRC2) recruitment. Together, our results identified the INO80-H2A.Z axis as an essential step for bivalent chromatin and poised gene expression and uncovered an epigenetic mechanism by which chromatin remodeling, histone variant, and histone modification coordinately control cell fate.
2021-07-04 | GSE158537 | GEO
Project description:INO80 is involved in many chromatin-dependent functions. However, its role in pluripotency has not been fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the primed state. Mechanistically, INO80 co-occupied gene promoters that were bivalently marked by H3K4me3 and H3K27me3. Further, its occupancy was required for H3K27me3 installation and maintenance, as well as downstream gene repression. Finally, INO80 promoted H2A.Z occupancy at the bivalent domains, which in turn facilitated the polycomb repressive complex 2 (PRC2) recruitment. Together, our results identified the INO80-H2A.Z axis as an essential step for bivalent chromatin and poised gene expression and uncovered an epigenetic mechanism by which chromatin remodeling, histone variant, and histone modification coordinately control cell fate.
2021-07-04 | GSE158528 | GEO
Project description:INO80 is involved in many chromatin-dependent functions. However, its role in pluripotency has not been fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the primed state. Mechanistically, INO80 co-occupied gene promoters that were bivalently marked by H3K4me3 and H3K27me3. Further, its occupancy was required for H3K27me3 installation and maintenance, as well as downstream gene repression. Finally, INO80 promoted H2A.Z occupancy at the bivalent domains, which in turn facilitated the polycomb repressive complex 2 (PRC2) recruitment. Together, our results identified the INO80-H2A.Z axis as an essential step for bivalent chromatin and poised gene expression and uncovered an epigenetic mechanism by which chromatin remodeling, histone variant, and histone modification coordinately control cell fate.
2021-07-04 | GSE158533 | GEO
Project description:Epigenetic priming factors establish a permissive epigenetic landscape which is not required until a later developmental or physiological time point, temporally uncoupling the presence of these factors with their phenotypic effects. One classic example of epigenetic priming is in the context of bivalent chromatin, found in pluripotent stem cells and early embryos at key developmental gene promoters marked by both activating-associated H3K4me3 and repressive-associated H3K27me3 histone modifications. It is currently unknown how these bivalent domains are targeted, or precisely how they impact on lineage commitment. Here we show that the small heterodimerising non-enzymatic DNA binding proteins Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) act as epigenetic priming factors to establish bivalency at a subset of developmental genes. Dppa2/4 localise to the +1 nucleosome position of bivalent genes and while they are not required for pluripotency in embryonic stem cells (ESCs), double knockout cells fail to exit pluripotency and to differentiate efficiently, with delays in upregulating bivalently marked lineage genes. Proteomics reveal that Dppa2/4 interact on chromatin with members of the COMPASS and Polycomb complexes important for H3K4me3 and H3K27me3 deposition, respectively. Epigenetic profiling reveals a striking loss of H3K4me3, H3K27me3, and their associated enzymatic machinery at a significant subset of bivalent promoters in Dppa2/4 mutants, in addition to loss of H2A.Z and chromatin accessibility. In wild-type ESCs, these “Dppa2/4-dependent” bivalent promoters are characterised by low H3K4me3 enrichment and breadth, near-absent expression levels and initiating but not elongating RNA polymerase. Notably, Dppa2/4-dependent promoters are less evolutionarily conserved suggesting that they lack additional safeguard measures to maintain bivalency at these genes in the absence of Dppa2/4. Concomitantly with the loss of bivalency, Dppa2/4-dependent bivalent promoters gain DNA methylation and consequently are no longer able to be effectively activated upon ESC differentiation, leading to defects in cell fate acquisition. Our findings reveal a targeting principle for bivalency to developmental gene promoters poising them for future lineage specific gene activation.
2020-05-26 | PXD014981 | Pride
Project description:Here we report the identification of ETHYLENE-INSENSITIVE6 (EIN6), which is a H3K27me3 demethylase also known as RELATIVE OF EARLY FLOWERING6 (REF6), and EIN6 ENHANCER (EEN), the Arabidopsis homolog of the yeast INO80 chromatin remodeling complex subunit IES6 (INO EIGHTY SUBUNIT6). By applying high-throughput profiling of histone modifications, histone variant occupancy, cytosine methylation and mRNA expression in various Arabidopsis mutants, we identified ETHYLENE-INSENSITIVE2 (EIN2) as a direct target of EIN6 (REF6) and EEN. EIN6 (REF6) and EEN as part of the INO80 complex interdependently and uniquely control the level and the localization of the repressive histone modification H3K27me3 and the histone variant H2A.Z at the 5’ untranslated region (5’UTR) intron of EIN2. Concomitant functional loss of EIN6 (REF6) and the INO80 complex shifts the chromatin landscape at EIN2 to a repressive state causing a dramatic reduction of EIN2 expression and subsequent collapse of the entire ethylene transcriptional cascade.
2019-08-19 | GSE122314 | GEO
Project description:To investigate the incorporation dynamics of histone variant H2A.Z, we determined its genomic localization at single nucleosome resolution, as well as the localization of its chromatin remodelers Swr1 and Ino80. We find that Swr1 binding alone is a poor predictor of H2A.Z occupancy levels, and that normal Swr1 and Ino80 localization are actually dependent on H2A.Z. Additionally, we find that H2A.Z’s bimodal incorporation on either side of the NDR is not a general feature of TSS, but is specifically a marker for bidirectional transcription, such that the upstream flanking -1 H2A.Z-containing nucleosome is more appropriately considered as a +1 H2A.Z nucleosome for antisense transcription.
2019-10-29 | GSE104147 | GEO
Project description:Nucleosomes, composed of DNA and histone proteins, represent the fundamental repeating unit of the eukaryotic genome; posttranslational modifications of these histone proteins influence the activity of the associated genomic regions to regulate cell identity. Traditionally, trimethylation of histone H3K4 (H3K4me3) is associated with transcriptional initiation, whereas trimethylation of H3K27 (H3K27me3) is transcriptionally repressive. The apparent juxtaposition of these opposing marks, termed “bivalent domains”, was proposed to specifically demarcate of small set transcriptionally-poised lineage-commitment genes that resolve to one constituent modification through differentiation, thereby determining transcriptional status. Since then, many thousands of studies have canonized the bivalency model as a chromatin hallmark of development in many cell types. However, these conclusions are largely based on chromatin immunoprecipitations (ChIP) with significant methodological problems hampering their interpretation. Absent direct quantitative measurements, it has been difficult to evaluate the strength of the bivalency model. Here, we present reICeChIP, a calibrated sequential ChIP method to quantitatively measure H3K4me3/H3K27me3 bivalency genome-wide, addressing the limitations of prior measurements. With reICeChIP, we profile bivalency through the differentiation paradigm that first established this model: from naïve mouse embryonic stem cells (mESCs) into neuronal progenitor cells (NPCs). Our results cast doubt on every aspect of the bivalency model; in this context, we find that bivalency is widespread, does not resolve with differentiation, and is neither sensitive nor specific for identifying poised developmental genes or gene expression status more broadly. Our findings caution against interpreting bivalent domains as specific markers of developmentally poised genes.
2021-09-10 | GSE183155 | GEO
Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
2017-03-31 | GSE89434 | GEO
Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
2017-03-31 | GSE89436 | GEO
Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
2017-03-31 | GSE89435 | GEO