Cla4 phosphorylates histone methyltransferase Set1 to prevent its degradation by the APC/CCdh1 complex
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ABSTRACT:
PROVIDER: PRJNA1000592 | ENA |
REPOSITORIES: ENA
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Project description:The expression of chromatin modifying enzymes needs to be tightly controlled to ensure proper distribution of chromatin modifications. H3 lysine 4 trimethylation (H3K4me3) is a conserved histone modification catalyzed by histone methyltransferase Set1 and its dysregulation is associated with pathologies. Here, we show that Set1 is intrinsically unstable and its protein levels are strictly controlled by ubiquitin-dependent proteasomal degradation within the cell cycle and during gene transcription. Specifically, Set1 contains a destruction box (D-box) that can be recognized by the E3 ligase APC/CCdh1 complex and degraded by the ubiquitin-proteasome pathway. Cla4 phosphorylates serine 228 (S228) within Set1 D-box, which inhibits APC/CCdh1-mediated Set1 proteolysis. During gene transcription, the RNA polymerase II-associated PAF complex facilitates Cla4 to phosphorylate Set1-S228 and protect the chromatin-bound Set1 from degradation. By modulating the stability of Set1, Cla4 and the APC/CCdh1 complex control H3K4me3 levels, which then regulates gene transcription, cell cycle progression and chronological aging. In addition to Set1, there are 141 proteins containing the D-box that can be potentially phosphorylated by Cla4 to prevent their degradation by the APC/CCdh1 complex. Thus, we not only addressed the long-standing question about how Set1 stability is controlled, but also uncovered a new mechanism to regulate protein stability
2023-10-18 | GSE239705 | GEO
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Gene expression changes were generated from five different yeast strains representing wild type control, set1 null and jhd2 null mutants, and wild type SET1 or dominant hyperacive SET1-G990E overexpressing mutants. Three independent biological samples were grown for each strain, total RNA was isolated, libraries were prepared, sequenced, and analyzed separately.
2016-06-15 | E-GEOD-73406 | biostudies-arrayexpress
Project description:Set1 H3K4 methyltransferase and Jhd2 H3K4 demethylase
| PRJNA296896 | ENA
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes.
2016-06-15 | GSE73406 | GEO
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylationâdemethylation control chromatin dynamics during various facets of transcriptional regulation. Genome-wide nucleosome maps were generated from three different yeast strains representing wild type control, set1 null and jhd2 null mutants. Three independent biological samples were grown for each strain, nucleosomes were prepared by micrococcal nuclease digestion, libraries were prepared, mononculeosomal DNA was isolated, sequenced, and analyzed separately.
2016-06-15 | E-GEOD-73404 | biostudies-arrayexpress
Project description:Purpose: Understand the synergistic relationship between the methyltransferases Set1 and Set5 in the regulation of gene expression. Methods: Total mRNA was obtained from two independent biological replicates each of wildtype (WT), set1∆, set5∆, SET5 Y402A and set1∆set5∆ S. cerevisiae strains. Libraries were generated and sequenced using an Illumina HiSeq2000 platform. The sequence reads that passed quality filters were mapped using TopHat and expression levels were quantified using Cufflinks. Results: We generated FPKM expression values for each transcript and identified the differentially expressed genes using an FDR-adjusted p-value of 0.05. Subsequent data analysis was restricted to genes with fold-change greater than 1.7 relative to WT. Our results show that Set1 and Set5 have roles primarily in transcription repression. Moreover, lack of both Set1 and Set5 results in a synergistic exhacerbation of the transcriptional derepression observed in the single mutants. Further analysis revealed a specific enrichment of the Set5/Set1-repressed genes near repetitive DNA sequences of the genome. Conclusions: Our study uncovers an unexpected synergistic role of Set1 and Set5 in transcription repression of telomeric regions and Ty retrotransposons. mRNA profiles of wildtype (WT), set1∆, set5∆, SET5 Y402A and set1∆set5∆ were generated by sequencing using an Illumina HiSeq2000 platform. Two biological replicates of each strain were used.
2014-01-15 | E-GEOD-52086 | biostudies-arrayexpress
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylationâdemethylation control chromatin dynamics during various facets of transcriptional regulation. Genome-wide nucleosome maps were generated from three different yeast strains representing no tag control, 8V5-Set1 and Jhd2-12V5. Cells were cross-linked with formaldehyde, spheroplasted, nuclei were isolated and chromatin was prepared using micrococcal nuclease digestion, chromatin immunoprecipitation was performed using an epitope-tag specific antibody, libraries were prepared from ChIP and input DNA, sequenced, and analyzed separately.
2016-06-15 | E-GEOD-81021 | biostudies-arrayexpress
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylationâ??demethylation control chromatin dynamics during various facets of transcriptional regulation. Genome-wide nucleosome maps were generated from three different yeast strains representing no tag control, 8V5-Set1 and Jhd2-12V5. Cells were cross-linked with formaldehyde, spheroplasted, nuclei were isolated and chromatin was prepared using micrococcal nuclease digestion , chromatin immunoprecipitation was performed using an epitope-tag specific antibody, libraries were prepared from ChIP and input DNA, sequenced, and analyzed separately.
2016-06-15 | E-GEOD-81022 | biostudies-arrayexpress
Project description:Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. We find combined activities of Set1 and Jhd2 via H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Providing mechanistic insights, our data reveal that Set1 and Jhd2 together control nucleosomal occupancy during transcriptional co-regulation. Moreover, we find a remarkable genome-wide co-regulation of nucleosome and chromatin structure by Set1 and Jhd2 at different groups of transcriptionally active or inactive genes and at different regions within yeast genes. Overall, our study prompts a model wherein combined actions of Set1 and Jhd2 via H3K4 methylation−demethylation control chromatin dynamics during various facets of transcriptional regulation.
2016-06-15 | GSE73404 | GEO
Project description:H3K4me3 is catalyzed by the Set1/MLL family of methyltransferases, whose function in catalyzing H3K4me3 is unique. Impaired function of Set1/MLL family members can lead to many abnormalities, such as bone and nerve defects, leukemia, and even death. Although the Set1 family plays an important regulatory role in various biological processes, it is still unclear how the Set1 protein itself is regulated and how protein levels are maintained. Due to the numerous homologues, complex composition, and high molecular weight of Set1 in higher organisms, especially humans, related research is greatly limited. In brewing yeast, Set1 is the only methyltransferase that catalyzes H3K4me3 and is highly conserved between species. Therefore, yeast is an ideal model for studying the functions and mechanisms of the Set1 family. In addition, Set1 protein plays an important role in regulating gene transcription, promoting telomere silencing, and maintaining cell lifespan. The Set1 family also plays an important regulatory role in the occurrence and development of various cancers.
2023-10-24 | PXD042010 | Pride