Histone acetylation recruits the SWR1 complex to regulate active DNA demethylation in Arabidopsis
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ABSTRACT:
PROVIDER: PRJNA473996 | ENA |
REPOSITORIES: ENA
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Project description:The eukaryotic genome is divided into regions of heterochromatin and euchromatin. The histone variant H2A.Z specifically localizes at euchromatin and displays a genome-wide anti-correlation with DNA methylation. DNA methylation plays a central role in the epigenetic regulation of many eukaryotic genomes. Active DNA demethylation is critical for controlling the epigenome in plants and mammals. Yet, little is known about how DNA demethylases are recruited to target loci. Here we report that SWR1, a conserved histone H2A.Z deposition complex, regulates DNA demethylation in Arabidopsis thaliana by recruiting the plant DNA demethylase ROS1. A forward genetic screen for anti-silencing mutants identified two SWR1 components, PIE1 and ARP6, as cellular factors required for ROS1-mediated DNA demethylation. We further discovered two bromodomain-containing proteins, the methyl-DNA-binding protein AtMBD9, and NPX1, a plant homolog of ScBDF1 in yeast, as components of the SWR1 complex in Arabidopsis. AtMBD9 and NPX1 function redundantly in preventing DNA hypermethylation and transcriptional gene silencing by recognizing histone acetylation marks established by IDM1, a known regulator of DNA demethylation. We show that IDM1 is required for H2A.Z deposition in many genomic regions targeted for active DNA demethylation. We found that H2A.Z interacts with ROS1 and is required for locus-specific DNA demethylation and antisilencing. Our results reveal a role of H2A.Z in active DNA demethylation, and a mechanism through which DNA demethylases can be recruited to target regions by specific histone acetylation marks.
2019-08-01 | GSE115170 | GEO
Project description:Active DNA demethylation is critical for controlling the DNA methylomes in plants and mammals. However, little is known about how DNA demethylases are recruited to target loci, and the involvement of chromatin marks in this process. Here, we identify 2 components of the SWR1 chromatin-remodeling complex, PIE1 and ARP6, as required for ROS1-mediated DNA demethylation, and discover 2 SWR1-associated bromodomain-containing proteins, AtMBD9 and nuclear protein X1 (NPX1). AtMBD9 and NPX1 recognize histone acetylation marks established by increased DNA methylation 1 (IDM1), a known regulator of DNA demethylation, redundantly facilitating H2A.Z deposition at IDM1 target loci. We show that at some genomic regions, H2A.Z and DNA methylation marks coexist, and H2A.Z physically interacts with ROS1 to regulate DNA demethylation and antisilencing. Our results unveil a mechanism through which DNA demethylases can be recruited to specific target loci exhibiting particular histone marks, providing a conceptual framework to understand how chromatin marks regulate DNA demethylation.
| S-EPMC6697875 | biostudies-literature
Project description:The SWR1 Complex Regulates Active DNA Demethylation in Arabidopsis
| PRJNA421283 | ENA
Project description:The histone variant H2A.Z marking permissive chromatin is preferentially deposited at promoter-proximal +1 nucleosomes by the multicomponent SWR1 chromatin remodeler. Although SWR1 targeting to nucleosome-depleted regions (NDRs) is directed by its free DNA length sensing module, how the remodeler is guided preferentially to flanking +1 nucleosomes has been enigmatic. Here, we show by live-cell, single-molecule tracking (SMT) that SWR1 subunits Bdf1 and Yaf9 harboring bromo and YEATS acetyl-histone reader domains are required for quantitative chromatin binding via distinct kinetic mechanisms: Bdf1 increases SWR1 association, Yaf9-YEATS reduces disassociation. Notably, SMT and genome-wide ChIP-exo reveals Bdf1 and Yaf9 contributions to SWR1 targeting globally and histone exchange at +1 nucleosomes. Our findings highlight the native biochemistry of histone readers and suggest a broadly applicable, two-stage mechanism wherein acetyl-histone interactions initially constrain 3D diffusion of SWR1 to increase local concentration, followed by stochastic 1D diffusion at NDRs with directional capture by acetylated +1 nucleosomes.
2024-07-29 | GSE273028 | GEO
Project description:The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. While the multi-subunit SWR1 chromatin remodeling complex is known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for competitive binding of di-nucleosome substrates revealed that SWR1 preferentially binds long nucleosome-free DNA adjoining core particles, allowing discrimination of gene promoters over gene bodies. We traced the critical DNA binding component of SWR1 to the conserved Swc2/YL1 subunit, whose activity is required for both SWR1 binding and H2A.Z incorporation in vivo. Histone acetylation by NuA4 enhances SWR1 binding, but the interaction with nucleosome-free DNA is the major determinant. ‘Hierarchical cooperation’ between high affinity DNA- and low affinity histone modification-binding factors may reconcile the large disparity in affinities for chromatin substrates, and unify classical control by DNA-binding factors with post-translational histone modifications and ATP-dependent nucleosome mobility. Swr1 TAP IF of various mutants
2013-09-16 | E-GEOD-49183 | biostudies-arrayexpress
Project description:Lin28, a well-known RNA-binding protein, regulates diverse cellular properties. All physiological functions of Lin28A characterized so far have been attributed to its repression of let-7 miRNA biogenesis or modulation of the mRNA translational efficiency. Here we show that Lin28A directly binds to a consensus DNA sequence in vitro and in mouse embryonic stem cells in vivo. ChIP-seq and RNA-seq reveal the enrichment of Lin28A binding around transcription start sites, and a positive correlation between its genomic occupancy and expression of many associated genes. Mechanistically, Lin28A recruits 5-methylcytosine-dioxygenase Tet1 to genomic binding sites to orchestrate 5-methylcytosine and 5-hydroxymethylcytosine dynamics. Either Lin28A or Tet1 knockdown leads to dysregulated DNA methylation and expression of common target genes. These results reveal a surprising role for Lin28A in transcriptional regulation via epigenetic DNA modifications and provide a new framework for understanding mechanisms underlying versatile functions of Lin28A in mammalian systems. Examine the DNA binding ability of Lin28 and its roles in regulating gene expression by coordinating with Tet1
2015-12-07 | E-GEOD-74254 | biostudies-arrayexpress
Project description:A characteristic feature of anaplastic large cell lymphoma (ALCL) is the significant reduction of the T-cell expression program despite its T-cell origin, a finding very similar to the loss of B-cell identity of classical Hodgkin lymphoma (cHL). Previously we demonstrated that epigenetic mechanisms are active in cHL to induce this peculiar phenotype. The results show that combined DNA demethylation and histone acetylation of T-cell lines induce an almost complete extinction of the T-cell phenotype, including the down-regulation of essential T-cell receptor signalling pathway genes such as CD3, LCK and ZAP70, as well as an up-regulation of ALCL-characteristic genes. In contrast, combined DNA demethylation and histone acetylation of ALCL cells is not able to reconstitute their T-cell phenotype. This clearly demonstrates that similar epigenetic mechanisms are active in ALCL and cHL which are responsible for the extinction of their cell type characteristic phenotype. We subjected T-cell lymphoma/leukemia cell lines and ALCL cell lines (n=4, each) to epigenetic modifiers to evoke DNA demethylation and the histone acetylation. Global gene expression profiling (Affymetrix) was performed from treated and untreated cell lines which were evaluated by real-time RT-PCR and Western Blot analysis.
2012-08-19 | E-GEOD-26101 | biostudies-arrayexpress
Project description:The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. While the multi-subunit SWR1 chromatin remodeling complex is known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for competitive binding of di-nucleosome substrates revealed that SWR1 preferentially binds long nucleosome-free DNA adjoining core particles, allowing discrimination of gene promoters over gene bodies. We traced the critical DNA binding component of SWR1 to the conserved Swc2/YL1 subunit, whose activity is required for both SWR1 binding and H2A.Z incorporation in vivo. Histone acetylation by NuA4 enhances SWR1 binding, but the interaction with nucleosome-free DNA is the major determinant. ‘Hierarchical cooperation’ between high affinity DNA- and low affinity histone modification-binding factors may reconcile the large disparity in affinities for chromatin substrates, and unify classical control by DNA-binding factors with post-translational histone modifications and ATP-dependent nucleosome mobility.
2013-09-16 | GSE49183 | GEO
Project description:Deposition of histone variant H2A.Z by the SWR1 chromatin-remodeling complex is critical for the appropriate expression of many genes in eukaryotes, yet, despite its importance, the composition of the Arabidopsis SWR1 complex has not been thoroughly analyzed. Here we have identified the interacting partners of a conserved Arabidopsis SWR1 subunit, actin-related protein 6 (ARP6). We isolated 9 predicted components, identifying subunits implicated in histone acetylation and interacting partners implicated in chromatin biology. We found that the methyl-CpG-binding domain 9 (MBD9) subunit functioned synergistically with ARP6 to control flowering time. MBD9, in combination with ARP6, was involved in the SWR1-mediated incorporation of the majority of H2A.Z. MBD6 was further required for deposition of H2A.Z at a distinct subset of loci. MBD9 was preferentially bound to nucleosome-depleted regions at the 5’ of genes containing high levels of activating histone marks. Our data suggests a model for MBD9 in recruiting the SWR1 complex to open chromatin of actively transcribing genes.
2019-06-21 | GSE123261 | GEO
Project description:Deposition of histone variant H2A.Z by the SWR1 chromatin-remodeling complex is critical for the appropriate expression of many genes in eukaryotes, yet, despite its importance, the composition of the Arabidopsis SWR1 complex has not been thoroughly analyzed. Here we have identified the interacting partners of a conserved Arabidopsis SWR1 subunit, actin-related protein 6 (ARP6). We isolated 9 predicted components, identifying subunits implicated in histone acetylation and interacting partners implicated in chromatin biology. We found that the methyl-CpG-binding domain 9 (MBD9) subunit functioned synergistically with ARP6 to control flowering time. MBD9, in combination with ARP6, was involved in the SWR1-mediated incorporation of the majority of H2A.Z. MBD6 was further required for deposition of H2A.Z at a distinct subset of loci. MBD9 was preferentially bound to nucleosome-depleted regions at the 5’ of genes containing high levels of activating histone marks. Our data suggests a model for MBD9 in recruiting the SWR1 complex to open chromatin of actively transcribing genes.
2019-06-21 | GSE123260 | GEO