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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE156217 | 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.

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 (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

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 (ATAC-seq_DRB)

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 | GSE173313 | GEO

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

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

| PRJNA657058 | ENA

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

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

| PRJNA725179 | ENA

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

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

| PRJNA657060 | ENA

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

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

| PRJNA657059 | ENA

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1.

Project description:Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.

| S-EPMC2742506 | biostudies-literature

Preferential dimethylation of histone H4 lysine 20 by Suv4-20.

Project description:Post-translational modifications of histone tails direct nuclear processes including transcription, DNA repair, and chromatin packaging. Lysine 20 of histone H4 is mono-, di-, or trimethylated in vivo, but the regulation and significance of these methylations is poorly understood. The SET domain proteins PR-Set7 and Suv4-20 have been implicated in mono- and trimethylation, respectively; however, enzymes that dimethylate lysine 20 have not been identified. Here we report that Drosophila Suv4-20 is a mixed product specificity methyltransferase that dimethylates approximately 90% and trimethylates less than 5% of total H4 at lysine 20 in S2 cells. Trimethylation, but not dimethylation, is reduced in Drosophila larvae lacking HP1, suggesting that an interaction with HP1 regulates the product specificity of Suv4-20 and enrichment of trimethyllysine 20 within heterochromatin. Similar to the Drosophila enzyme, human Suv4-20h1/h2 enzymes generate di- and trimethyllysine 20. PR-Set7 and Suv4-20 are both required for normal levels of methylation, suggesting they have non-redundant functions. Alterations in the level of lysine 20 methylation following knock-down or overexpression of Suv4-20 did not affect lysine 16 acetylation, revealing that these two modifications are not competitive in vivo. Depletion of Suv4-20h1/h2 in HeLa cells impaired the formation of 53BP1 foci, suggesting dimethyllysine 20 is required for a proper DNA damage response. Collectively, the data indicate that Suv4-20 generates nearly ubiquitous dimethylation that facilitates the DNA damage response and selective trimethylation that is involved in heterochromatin formation.

| S-EPMC2335358 | biostudies-literature

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