Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19884 | GEO | 2010/08/09
SECONDARY ACCESSION(S): PRJNA122023
REPOSITORIES: GEO
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Project description:Both, acetylation of histones and of histone variant H2A.Z are conserved features of eukaryotic transcription start sites (TSSs) and both features appear to be critical for correct transcription initiation. However, complex patterns of transcriptional regulation have complicated the establishment of functional links between histone acetylation, H2A.Z deposition and their importance in transcription regulation. To elucidate these links, we took advantage of the unusual genome organization in Trypanosoma brucei, a highly divergent eukaryote. In T. brucei genes are organized in long polycistronic transcription units, drastically reducing the sites of transcription initiation. Employing a highly sensitive and quantitative mass-spectrometry-based approach, we quantified the genome-wide histone acetylation and methylation pattern and identified various acetyl and methyl marks exclusively enriched at TSSs In addition, we show that deletion of histone acetyltransferase 2 results in a loss of H4 acetylation at TSSs, a loss of H2A.Z deposition at TSSs and a shift in the sites of transcription initiation. Combined, our findings demonstrate an evolutionary conserved link between histone H4 acetylation, H2A.Z deposition and RNA transcription initiation.
2020-03-24 | PXD014452 | Pride
Project description:H2A.Z is an evolutionarily conserved H2A variant implicated in the regulation of gene expression, however its role in transcriptional deregulation in cancer remains poorly understood. Using genome-wide studies, we investigated the role of promoter-associated H2A.Z and acetylated H2A.Z (acH2A.Z) in gene deregulation and its relationship with DNA methylation and H3K27me3 in prostate cancer. Our results reconcile the conflicting reports of positive and negative roles for histone H2A.Z and gene expression states. We find that H2A.Z is enriched in a bimodal distribution at nucleosomes surrounding the transcription start sites (TSSs) of both active and poised gene promoters, whereas acH2A.Z is only localized at the TSSs of actively expressed genes. Interestingly, H2A.Z spreads across the entire promoter of inactive genes in a de-acetylated state. Gene deregulation in cancer is also associated with a reorganization of acH2A.Z and H2A.Z nucleosome occupancy across the promoter region and TSS of genes. Notably, in cancer cells we find that a gain of acH2A.Z at the TSS occurs with an overall decrease of H2A.Z levels in concert with oncogene activation. Furthermore, underacetylated H2A.Z at TSSs is increased with silencing of tumour suppressor genes. We also demonstrate that acH2A.Z anti-correlates with promoter H3K27me3 and DNA methylation. For the first time, we show that acetylation of H2A.Z is a key modification involved in gene activity in normal cells and in epigenetic gene deregulation in tumourigenesis.
2011-07-13 | GSE25914 | GEO
Project description:Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis
| PRJNA122023 | ENA
Project description:Eukaryotic chromatin is separated into functional domains differentiated by posttranslational histone modifications, histone variants, and DNA methylation. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are critical for eukaryotic development, and aberrant methylation-induced silencing of tumor suppressor genes is a common feature of human cancer. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5' ends of genes where it promotes transcriptional competence. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana, regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation, engenders opposite changes in H2A.Z deposition, while mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z17 leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation. Keywords: Affinity-purification on microarray All experiments were done using two channels per chip. DNA methylation experiments compared immunoprecipitated, methylated DNA to control genomic DNA. H2A.Z experiments compared whole micrococcal nuclease-treated affinity-purified chromatin to input chromatin used for affinity purification. Affinity purification was performed using either biotin-tagged H2A.Z, pulled down using streptavidin, or endogenous H2A.Z pulled down using an anti-H2A.Z antibody.
2008-10-02 | E-GEOD-12212 | biostudies-arrayexpress
Project description:Eukaryotic chromatin is separated into functional domains differentiated by posttranslational histone modifications, histone variants, and DNA methylation. Methylation is associated with repression of transcriptional initiation in plants and animals, and is frequently found in transposable elements. Proper methylation patterns are critical for eukaryotic development, and aberrant methylation-induced silencing of tumor suppressor genes is a common feature of human cancer. In contrast to methylation, the histone variant H2A.Z is preferentially deposited by the Swr1 ATPase complex near 5' ends of genes where it promotes transcriptional competence. How DNA methylation and H2A.Z influence transcription remains largely unknown. Here we show that in the plant Arabidopsis thaliana, regions of DNA methylation are quantitatively deficient in H2A.Z. Exclusion of H2A.Z is seen at sites of DNA methylation in the bodies of actively transcribed genes and in methylated transposons. Mutation of the MET1 DNA methyltransferase, which causes both losses and gains of DNA methylation, engenders opposite changes in H2A.Z deposition, while mutation of the PIE1 subunit of the Swr1 complex that deposits H2A.Z17 leads to genome-wide hypermethylation. Our findings indicate that DNA methylation can influence chromatin structure and effect gene silencing by excluding H2A.Z, and that H2A.Z protects genes from DNA methylation. Keywords: Affinity-purification on microarray
2008-10-03 | GSE12212 | 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:The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that a loss of H2A.Z in Arabidopsis does not affect the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is caused by the exclusion of H2A.Z from methylated DNA. RNA-seq and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. We find that a loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to both endogenous and exogenous stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes. Examination of DNA methylation and transcription in an h2a.z mutant
2012-12-13 | E-GEOD-39045 | biostudies-arrayexpress
Project description:Tissue and their component cells have unique DNA methylation profiles comprising DNA methylation patterns of tissue-dependent and differentially methylated regions (T-DMRs). T-DMRs are found throughout the genome and influence tissue-specific gene expression. DNA methylation profile of T-DMRs underlies the network of tissue- and developmental stage-specific transcription factors and their targets. The adult brain consists of various kinds of cells that sequentially appear as neurons, astrocytes, and oligodendrocytes from late gestation through the neonatal period. Distinctive neural progenitor cells (NPCs) that exhibit different differentiation poteintials to neurons to glial cells are generated during mid-to-late gestation. To explore DNA methylation profiles of mouse NPCs, we compared neurospheres derived from telencephalons at embryonic day 11.5 (E11.5NSph) and 14.5 (E14.5NSph) by T-DMR profiling with restriction tag-mediated amplification (D-REAM) combined with Affymetrix GeneChip Mouse Promoter 1.0R Array. We used HpyCH4IV, a methylation-sensitive restriction enzyme that recognizes ACGT residues. Because these are uniformly distributed across the genome, it enables less biased analysis. By comparing D-REAM data between E11.5NSph and E14.5NSph, we identified genes with T-DMRs including those involved in neural develpment and/or associated with neurological disorders in humans. The present study elucidates the underlying dynamics of the DNA methylation profile of T-DMRs during neural development, including insights into developmental stage-specific hypomethylation of T-DMRs around TSSs.
2012-12-01 | E-MTAB-1150 | biostudies-arrayexpress
Project description:The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that a loss of H2A.Z in Arabidopsis does not affect the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is caused by the exclusion of H2A.Z from methylated DNA. RNA-seq and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. We find that a loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to both endogenous and exogenous stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes.
2012-12-13 | GSE39045 | GEO
Project description:Transposable elements (TEs) are largely inactive. Interestingly, a subset of TEs are naturally expressed in the vegetative cell (VC) of the male gametophyte, pollen in Arabidopsis. However, the extent and mechanism of such TE activation were unknown. Through RNA-seq, we identified pollen-activated TEs and annotated the transcriptional start sites (TSSs) and transcriptional termination sites (TTSs) using a program called Mikado. We have previously shown that H1 is expressed in sperm but not in VC, which prompted us to ectopically express H1 in VC for studying TE regulation through RNA-seq and bisulfite-seq. Our RNA-seq data shows that H1 expression in VC represses some of pollen-activated TEs. Furthermore, bisulfite-seq data from the pollen nuclei isolated via fluorescence-activated cell sorting (FACS) shows that H1 expression in VC increases DNA methylation of some of H1-repressed TEs around their TSSs, while leaving other H1-repressed TEs unchanged in DNA methylation. Our results indicate that H1 represses TE expression through both DNA methylation-dependent and -independent mechanisms and that natural depletion of H1 in VC allows TEs to be activated.
2019-05-29 | GSE120519 | GEO