Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inheritance of Repressed Chromatin Domains during S-phase Requires the Histone Chaperone NPM1

ABSTRACT: The epigenetic process safeguards cell identity during cell division through the inheritance of appropriate gene expression profiles. We demonstrated previously that parental nucleosomes are inherited by the same chromatin domains during DNA replication only in the case of repressed chromatin. We now show that this specificity is conveyed by NPM1, a histone H3/H4 chaperone. Proteomic analyses of late S-phase chromatin revealed NPM1 in association with both H3K27me3, an integral component of facultative heterochromatin and MCM2, an integral component of the DNA replication machinery; moreover NPM1 interacts directly with PRC2 and with MCM2. Given that NPM1 is essential, the inheritance of repressed chromatin domains was examined anew using mESCs expressing an auxin-degradable version of endogenous NPM1. Upon NPM1 degradation, cells accumulated in S-phase of the cell-cycle and parental nucleosome inheritance from repressed chromatin domains was markedly compromised. Appropriate inheritance required the NPM1 acidic patches that function in chaperone activity, pointing to NPM1 being integral to the epigenetic process.

ORGANISM(S): Mus musculus

PROVIDER: GSE183090 | GEO | 2022/04/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Inheritance of Repressed Chromatin Domains during S-phase Requires the Histone Chaperone NPM1

Project description:Inheritance of Repressed Chromatin Domains during S-phase Requires the Histone Chaperone NPM1

| PRJNA759176 | ENA

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance

Project description:Chromatin-based epigenetic memory relies on the accurate distribution of parental histone tetramers to newly replicated DNA strands, serving as templates for chromatin structure duplication. Mcm2, a subunit of the replicative helicase, and the Dpb3/4, subunits of polymerase epsilon, govern parental histone deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here we show in fission yeast that a Mcm2 histone chaperone mutation severely disrupts heterochromatin inheritance, while Dpb3/4 mutations cause only moderate defects. Surprisingly, simultaneous Mcm2 and Dpb3/4 mutations stabilizes heterochromatin inheritance. eSPAN analyses confirm the conservation of Mcm2 and Dpb3/4 functions in parental histone segregation, with their collective absence reducing segregation bias. Furthermore, the FACT histone chaperone also regulates parental histone transfer independently of strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone density, ensuring faithful heterochromatin inheritance. These results underscore the importance of precise parental histone segregation to the lagging strand for epigenetic inheritance and unveil unique properties of parental histone chaperones during DNA replication.

2024-04-17 | GSE237770 | GEO

Quantification of histone H3 and H4 modifications by mass spectrometry in wildtype and MCM2-2A mutants of mice ESCs

Project description:During DNA replication modified parental histones H3-H4 are segregated almost symmetrically to the two daughter DNA strands enabling mitotic inheritance of histone PTMs. Whether heritable histone modifications confer epigenetic regulation by maintaining chromatin states and gene expression is unclear. Using MCM2 histone-binding mutant embryonic stem cells (ESCs) and mass spectrometry, we show that asymmetric segregation of parental histones to the leading strand causes imbalanced inheritance of histone H3K27 methylations to daughter cells.

2023-08-30 | PXD020326 | Pride

DNA Polymerase Delta Governs Parental Histone Transfer to DNA Replication Lagging Strand

Project description:Chromatin replication is intricately intertwined with DNA replication, and the recycling of parental histones is essential for epigenetic inheritance. The transfer of parental histones to both the DNA replication leading and lagging strands involves two distinct pathways: the leading strand utilizes DNA polymerase ε subunits Dpb3/Dpb4, while the lagging strand is facilitated by the MCM helicase subunit Mcm2. However, the process by which Mcm2, moving along the leading strand, facilitates the transfer of parental histones to the lagging strand remains unclear. Our study reveals that the deletion of Pol32, a non-essential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the replication leading strand. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted by the mutation of Mcm2's histone H3-H4 binding domain. In conclusion, our findings identify the DNA polymerase delta subunit Pol32 as a novel key histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.

2024-04-24 | GSE252049 | GEO

Proper parental histone allocation is required for mouse embryonic stem cell differentiation and histone post-transcription modification inheritance

Project description:To understand whether parental histone PTM landscape plays roles in cell differentiation, we perturbed parental histone PTM allocation by mutating histone chaperone MCM2 on its histone binding domain (MCM2-2A mutation), disrupted only the histone transferring of MCM2 protein in mouse embryonic stem cells (ESCs). Combining single-cell transcriptomics and epigenomics with lineage barcoding, we found that MCM2-2A mutant ESCs cannot be fully differentiated to neuronal precursor cells (NPCs), causing by the redistribution of H3K27me3, and subsequently NPC related gene expression. Here, we show that the parental histone allocation plays an important role in the establishment of chromatin landscapes, altering ESC differentiational potential, shaping expression programs and cell heterogeneity.

2023-05-15 | GSE185271 | GEO

Mcm2 promotes stem cell differentiation via its ability to bind H3-H4 (RNA-Seq)

Project description:Mcm2, a subunit of the Mcm2-7 helicase best known for its role in DNA replication, contains a histone binding motif that facilitates the transfer of parental histone following DNA replication. Here we show that Mcm2 is important for the differentiation of mouse embryonic stem (ES) cells. Mcm2-2A mutation defective in histone binding impairs differentiation and programmatic changes in gene expression and histone modifications during differentiation. Mcm2 localizes at the transcription starting sites and the binding of Mcm2 at gene promoters is disrupted in both Mcm2-2A ES cells and neuro-precursor cells (NPCs). Reduced Mcm2 binding in Mcm2-2A ES cells correlates with decreased chromatin accessibility at bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications in NPCs. Together, our studies reveal a novel function of Mcm2 in ES differentiation, likely through manipulating chromatin landscape at bivalent chromatin domains.

2022-11-16 | GSE203271 | GEO

Mcm2 promotes stem cell differentiation via its ability to bind H3-H4 (ChIP-Seq)

2022-11-16 | GSE203270 | GEO

Quantification of parental and new histones H3, H4 and H2A by mass spectrometry: analysis of their dynamics along cell cycle progression in WT and MCM2-2A mutant mouse ESCs

Project description:During DNA replication parental, nucleosomic histones are segregated almost symmetrically to the two daughter DNA strands enabling mitotic inheritance of histones and their PTMs. In MCM2 histone-binding mutant ESCs (MCM2-2A), histones are recycled asymmetrically to the leading strand. To evaluate if loss of parental histones contributes to the asymmetry, we tracked new and old histones quantitatively by pulse-Triple-SILAC-MS. The quantification showed no change in dilution and incorporation dynamics in MCM2-2A cells, demonstrating that parental histones are not lost at replication forks but re-routed from the lagging to the leading strand.

2023-08-30 | PXD030364 | Pride

Active and repressed chromatin domains exhibit distinct nucleosome segregation during DNA replication

Project description:Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. Yet, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at single desired loci in mouse embryonic stem cells such that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through the local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment in the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.

2019-10-31 | GSE136245 | GEO

Defective transfer of parental histone decreases frequency of homologous recombination in budding yeast

Project description:Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging DNA strands, respectively. Single Dpb3 deletion (dpb3[DELTA]) or Mcm2 mutation (mcm2-3A), which each disrupt one parental histone transfer pathway, leads to the other[prime]s predominance. However, the impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeast Saccharomyces cerevisiae to determine the genetic and epigenetic outcomes from disruption of parental histone H3-H4 tetramer transfer. We found that a dpb3[DELTA]/mcm2-3A double mutant did not exhibit the single dpb3[DELTA] and mcm2-3A mutants[prime] asymmetric parental histone patterns, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower in dpb3[DELTA], mcm2-3A, and dpb3[DELTA]/mcm2-3A mutants relative to the wild-type strain, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones to the leading and lagging strands during DNA replication is essential for maintaining chromatin structure and that high levels of free histones due to parental histone transfer defects are detrimental to cells.

2024-04-24 | GSE240331 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data