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Histone H4 lysine 20 mono-methylation directly facilitates chromatin ‘openness’ and promotes transcription of housekeeping genes (ATAC-seq_DRB)

ABSTRACT: To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in synchronized and asynchronous Human Osteosarcoma U2OS and asynchronous Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173313 | GEO | 2021/06/04

REPOSITORIES: GEO

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Histone H4 lysine 20 mono-methylation directly facilitates chromatin ‘openness’ and promotes transcription of housekeeping genes (ATAC-seq)

Project description:To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in synchronized and asynchronous Human Osteosarcoma U2OS and asynchronous Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.

2021-06-04 | GSE156215 | GEO

Histone H4 lysine 20 mono-methylation directly facilitates chromatin ‘openness’ and promotes transcription of housekeeping genes (ChIP-seq)

Project description:To study the role of Histone H4 lysine 20 mono- and tri-methylation (H4K20me1, H4K20me3) in relationship to chromatin accessibility and gene expression, we report the application of high-throughput profiling of these marks in Human Osteosarcoma U2OS and Mouse Fibroblast (MEF) cells with Set8 knockdown or control siRNA treatment. We find that H4K20me1 contributes to the open chromatin structure at active genes.

2021-06-04 | GSE156216 | GEO

Poly ADP-ribosylation of SET8 leads to aberrant H4K20 methylation domains in mammalian cells

Project description:In mammalian cells, SET8 mediated Histone H4 Lys 20 monomethylation (H4K20me1) has been implicated in regulating mitotic condensation, DNA replication, DNA damage response, and gene expression. Here we show SET8, the only known enzyme for H4K20me1 is post-translationally poly ADP-ribosylated by PARP1 on lysine residues. PARP1 interacts with SET8 in a cell cycle- dependent manner. Poly ADP-ribosylation on SET8 renders it catalytically compromised and it undergoes degradation via ubiquitylation pathway. Knockdown of PARP1 shifted the relative dynamic equilibrium of H4K20me2 to H4K20me3 in cells. Overexpression or knockdown of PARP1 led to aberrant H4K20me1 domains genome-wide, impacting Wnt signaling pathways genes and transcription factor binding site enrichment. Therefore, SET8 mediated chromatin remodeling in mammalian cells are influenced by poly ADP-ribosylation by PARP1.

2022-11-17 | GSE188744 | GEO

Histone H4 lysine 20 mono-methylation directly facilitates chromatin openness and promotes transcription of housekeeping genes.

Project description:Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, we describe a divergent role for histone H4 lysine 20 mono-methylation (H4K20me1) and demonstrate that it directly facilitates chromatin openness and accessibility by disrupting chromatin folding. Thus, accumulation of H4K20me1 demarcates highly accessible chromatin at genes, and this is maintained throughout the cell cycle. In vitro, H4K20me1-containing nucleosomal arrays with nucleosome repeat lengths (NRL) of 187 and 197 are less compact than unmethylated (H4K20me0) or trimethylated (H4K20me3) arrays. Concordantly, and in contrast to trimethylated and unmethylated tails, solid-state NMR data shows that H4K20 mono-methylation changes the H4 conformational state and leads to more dynamic histone H4-tails. Notably, the increased chromatin accessibility mediated by H4K20me1 facilitates gene expression, particularly of housekeeping genes. Altogether, we show how the methylation state of a single histone H4 residue operates as a focal point in chromatin structure control. While H4K20me1 directly promotes chromatin openness at highly transcribed genes, it also serves as a stepping-stone for H4K20me3-dependent chromatin compaction.

| S-EPMC8379281 | biostudies-literature

Histone H4 lysine 20 mono-methylation directly facilitates chromatin ‘openness’ and promotes transcription of housekeeping genes

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-04 | GSE156217 | GEO

Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation [RNA-Seq]

Project description:Mono-methylation of Lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me-binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8null, H4K20R/A, and l(3)mbt mutant Drosophila melanogaster. We found that the gene expression profiles of H4K20A and H4K20R larvae are markedly different than Set8null larvae despite similar reductions in H4K20me1. Set8null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4K20 indicating that the developmental defects of Set8null animals are largely due to H4K20me1-independent effects on gene expression. Further, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8null and H4K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin, and therefore that H4K20me1 does not play a large role in gene expression.

2024-06-07 | GSE268821 | GEO

Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation [H4K20me1_CUT&RUN]

2024-06-07 | GSE268819 | GEO

Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation [GFP-L3mbt_CUT&RUN]

2024-06-07 | GSE268820 | GEO

Distinct H4-K20 methylation states time DNA replication initiation in mammalian cells

Project description:The role of histone modifications in DNA replication remains poorly understood. Here, we show that histone H4K20 monomethylation (me1) favors the assembly of the pre-replication complex on chromatin, an association that is increased when H4K20me1 is converted to trimethylation (H4K20me3). Remarkably, these histone methylations enhance origin activity, indicating a positive role in both origin licensing and activation. Genome-wide approaches revealed that H4K20me1 and H4K20me3 are enriched in distinct GC-rich regions, where their presence correlates with early-replicating and late-firing origins respectively. Accordingly, depletion of H4K20me1 at early origins delays the replication of active chromatin. Conversely, loss of H4K20me2/3 causes a drop in the licensing and activity of late-firing origins, slowing down the replication of heterochromatin. Altogether, these results suggest that the concerted activity of mammalian H4K20 methyltransferases and the resulting distribution of H4K20me states are essential to ensure the order and replication timing of different chromatin states.

2017-05-31 | GSE82065 | GEO

Histone 4 Lys-20 Mono-Methylation by SET8 Mediates Wnt Target Gene Activation

Project description:Histone methylation has an important role in transcriptional regulation. However, unlike H3K4 and H3K9 methylation, the role of H4K20 mono-methylation (H4K20me-1) in transcriptional regulation remains unclear. Here we show that Wnt3a specifically stimulates H4K20 mono-methylation at TBE (TCF-binding element) via the histone methylase SET8. Additionally, SET8 is crucial for activation of the Wnt reporter gene and target genes in both mammalian cells and zebrafish. Furthermore, SET8 interacts with TCF4/LEF1 directly, and this interaction is regulated by Wnt3a. Therefore, we conclude that SET8 is a Wnt signaling mediator and is recruited by LEF1/TCF4 to regulate the transcription of Wnt-activated genes, possibly via H4K20 mono-methylation at the target gene promoters. Our findings also indicate that H4K20me-1 is a marker for gene transcription activation, at least in canonical Wnt signaling. This chip experiment was carried out to find out how many genes would be regulated by SET8 after Wnt3a CM stimulated HEK293 cells. Total RNA was extracted from HEK293 cells after siRNA transfection (control or SET8 shRNA) for about 40 hours and then induced with Control or Wnt3a CM for 7 hours using TRIzol (Invitrogen) and the RNeasy kit (Qiagen). Three pairs of samples: si-control + control CM / si-control + Wnt3a CM 7 h / si-SET8 + Wnt3a CM. Samples were amplified and labeled using a NimbleGen One-Color DNA Labeling Kit.

2010-12-29 | E-GEOD-24708 | biostudies-arrayexpress

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