DEK controls the trade-off between growth and arrest via H2A.Z-nucleosomes in Arabidopsis
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PROVIDER: PRJNA468415 | ENA |
REPOSITORIES: ENA
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Project description:The decision of whether to grow and proliferate or to restrict growth and develop resilience to stress is a key biological trade-off. Multiple tumour suppressors have roles in suppressing growth and proliferation when conditions are unfavourable, and aggressive tumours show re-wiring of the metabolic pathways and removal of these restraints on growth1,2. In plants, constitutive growth results in increased sensitivity to environmental stress3,4. However, the underlying mechanisms controlling this decision are not well understood. We used temperature as a cue to discover regulators of this process in plants, as it both enhances growth and development rates within a specific range, and is also a stress at extremes. We find the conserved chromatin protein DEK plays a central role in balancing the response between growth and arrest in Arabidopsis, and it does this via H2A.Z-nucleosomes. DEK target genes show two distinct categories of chromatin architecture, and these predict induction or repression by DEK. We show that these chromatin signatures of DEK target genes might be conserved in human cells, suggesting that DEK may act through a fundamental evolutionarily conserved mechanism to control the balance between growth and arrest in plants and animals.
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Project description:The decision of whether to grow and proliferate or to restrict growth and develop resilience to stress is a key biological trade-off. Multiple tumour suppressors have roles in suppressing growth and proliferation when conditions are unfavourable, and aggressive tumours show re-wiring of the metabolic pathways and removal of these restraints on growth. In plants, constitutive growth results in increased sensitivity to environmental stress. However, the underlying mechanisms controlling this decision are not well understood. We used temperature as a cue to discover regulators of this process in plants, as it both enhances growth and development rates within a specific range, and is also a stress at extremes. We find the conserved chromatin protein DEK plays a central role in balancing the response between growth and arrest in Arabidopsis, and it does this via H2A.Z-nucleosomes. DEK target genes show two distinct categories of chromatin architecture, and these predict induction or repression by DEK. We show that these chromatin signatures of DEK target genes might be conserved in human cells, suggesting that DEK may act through a fundamental evolutionarily conserved mechanism to control the balance between growth and arrest in plants and animals.
2024-05-01 | GSE114641 | GEO
Project description:The decision of whether to grow and proliferate or to restrict growth and develop resilience to stress is a key biological trade-off. Multiple tumour suppressors have roles in suppressing growth and proliferation when conditions are unfavourable, and aggressive tumours show re-wiring of the metabolic pathways and removal of these restraints on growth. In plants, constitutive growth results in increased sensitivity to environmental stress. However, the underlying mechanisms controlling this decision are not well understood. We used temperature as a cue to discover regulators of this process in plants, as it both enhances growth and development rates within a specific range, and is also a stress at extremes. We find the conserved chromatin protein DEK plays a central role in balancing the response between growth and arrest in Arabidopsis, and it does this via H2A.Z-nucleosomes. DEK target genes show two distinct categories of chromatin architecture, and these predict induction or repression by DEK. We show that these chromatin signatures of DEK target genes might be conserved in human cells, suggesting that DEK may act through a fundamental evolutionarily conserved mechanism to control the balance between growth and arrest in plants and animals.
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Project description:Nucleosomes are barriers to transcription in vitro, however, their effects on RNA polymerase in vivo are unknown. Here we describe a simple and general strategy to comprehensively map the positions of elongating and arrested RNA Polymerase II (RNAPII) at nucleotide resolution. Our results suggest that nucleosomes present significant, context-specific barriers to RNAPII in vivo that can be tuned by the incorporation of H2A.Z. 8 sets of two replicates each of paired-end and 3 sets of two replicates each of single-end samples were sequenced and analyzed.
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Project description:Nucleosomes are barriers to transcription in vitro, however, their effects on RNA polymerase in vivo are unknown. Here we describe a simple and general strategy to comprehensively map the positions of elongating and arrested RNA Polymerase II (RNAPII) at nucleotide resolution. Our results suggest that nucleosomes present significant, context-specific barriers to RNAPII in vivo that can be tuned by the incorporation of H2A.Z.
2014-03-06 | GSE49106 | GEO
Project description:H2A.Z mono-ubiquitylation has been linked to transcriptional repression, but the mechanisms involved are not well understood. To address this, we developed a biotinylation-based approach to purify ubiquitylated H2A.Z (H2A.Zub) mononucleosomes for biochemical and genomics analyses. We observe that H2A.Zub nucleosomes are enriched for the repressive histone post-translational modification H3K27me3, but depleted of H3K4 methylation and other modifications associated with active transcription. ChIP-Seq analyses reveal that H2A.Zub-nucleosomes are enriched over non-expressed genes, and suggest that it is the relative ratio of ubiquitylated to non-ubiquitylated H2A.Z, rather than absolute presence or absence of H2A.Z ubiquitylation, that correlates with gene silencing. Finally, we observe that H2A.Zub-eniched mononucleosomes preferentially co-purify with transcriptional silencing factors as well as proteins involved in higher order chromatin organization such as CTCF and cohesin. Collectively, these results suggest an important role for H2A.Z ubiquitylation in mediating transcriptional regulation through its recruitment of transcriptional silencing factors and nuclear architectural proteins.
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Project description:Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or no H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity of SWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction. Total nucleosomes from MNase-treated nuclear extracts were fractionated by sequential immunoprecipitation into homotypic H2A/H2A (AA), heterotypic H2A/H2A.Z (AZ), and homotypic H2A.Z/H2A.Z (ZZ) nucleosomes.
2010-10-12 | E-GEOD-24618 | biostudies-arrayexpress
Project description:The chromatin remodelers (CRs) SWI/SNF and RSC function in evicting promoter nucleosomes at highly expressed yeast genes, particularly those activated by transcription factor Gcn4. Ino80 remodeling complex (Ino80C) can establish nucleosome-depleted regions (NDRs) in reconstituted chromatin, and was implicated in removing histone variant H2A.Z from the -1 and +1 nucleosomes flanking NDRs; however, Ino80C’s function in transcriptional activation in vivo is not well understood. Analyzing the cohort of Gcn4-induced genes in ino80Δ mutants has uncovered a role for Ino80C on par with SWI/SNF in evicting promoter nucleosomes and transcriptional activation. Compared to SWI/SNF, Ino80C generally functions over a wider region, spanning the -1 and +1 nucleosomes, NDR, and proximal genic nucleosomes, at genes highly dependent on its function. Defects in nucleosome eviction in ino80Δ cells are frequently accompanied by reduced promoter occupancies of TBP, and diminished transcription; and Ino80 is enriched at genes requiring its remodeler activity. Importantly, nuclear depletion of Ino80 impairs promoter nucleosome eviction even in a mutant lacking H2A.Z. Thus, Ino80C acts widely in the yeast genome together with RSC and SWI/SNF in evicting promoter nucleosomes and enhancing transcription, all in a manner at least partly independent of H2A.Z editing.
2019-12-24 | GSE142273 | GEO
Project description:In eukaryotes, DNA wraps around histones to form nucleosomes, which are compacted into chromatin. DNA-templated processes, including transcription, require chromatin disassembly and reassembly mediated by histone chaperones. Additionally, distinct histone variants can replace core histones to regulate chromatin structure and function. Although replacement of H2A with the evolutionarily conserved H2A.Z via the SWR1 histone chaperone complex has been extensively studied, in plants little is known about how a reduction of H2A.Z levels can be achieved. Here, we show that NRP proteins cause a decrease of H2A.Z-containing nucleosomes in Arabidopsis under standard growing conditions. nrp1-1 nrp2-2 double mutants show an over-accumulation of H2A.Z genome-wide, especially at heterochromatic regions normally H2A.Z-depleted in wild-type plants. Our work suggests that NRP proteins regulate gene expression by counteracting SWR1, thereby preventing excessive accumulation of H2A.Z.
2020-05-18 | PXD019248 | Pride
Project description:Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or no H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity of SWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction.
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