Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DOT1L regulates pericentromeric heterochromatin

ABSTRACT: Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell Line, Embryonic Stem Cell

SUBMITTER: TuKiet Lam

LAB HEAD: TuKiet Lam

PROVIDER: PXD028824 | Pride | 2023-05-26

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Mediator directs co-transcriptional heterochromatin assembly by RNAi-dependent and -independent pathways.

Project description:Background: Heterochromatin at the pericentromeric repeats in fission yeast is assembled and spread by an RNAi-dependent mechanism, which is coupled to the transcription of non-coding RNA from the repeats by RNA polymerase II. In addition, Rrp6, a component of the nuclear exosome, also contributes to heterochromatin assembly and is coupled to non-coding RNA transcription. The multi-subunit complex Mediator, which directs initiation of RNA polymerase II-dependent transcription, has recently been suggested to function after initiation in processes such as elongation of transcription and splicing. However, the role of Mediator in the regulation of chromatin structure is not well understood. Results: We investigated the role of Mediator in pericentromeric heterochromatin formation and found that deletion of specific subunits of the head domain of Mediator compromised heterochromatin structure. The Mediator head domain was required for Rrp6-dependent heterochromatin nucleation at the pericentromere and for RNAi-dependent spreading of heterochromatin into the neighboring region. In the latter process, Mediator appeared to contribute to efficient processing of siRNA from transcribed non-coding RNA, which was required for efficient spreading of heterochromatin. Furthermore, the head domain directed efficient transcription in heterochromatin. Conclusions: These results reveal a pivotal role for Mediator in multiple steps of transcription-coupled formation of pericentromeric heterochromatin. This observation further extends the role of Mediator to co-transcriptional chromatin regulation. Gene expression profile at exponentially-growing phase.in the fission yeast deletion mutants of pmc6, med20 and dcr1.

2013-08-31 | E-GEOD-43543 | biostudies-arrayexpress

Genomic and genetic characterization of rice Cen3 reveals evolutionary remnants of a complex centromere (mRNA data)

Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. MPSS was performed to sequence small RNAs that derived from 16 untreated and 6 abiotic-treated diverse tissue libraries. The method for the MPSS sequencing of mRNAs is described in Brenner et al. (Nat Biotechnol. 2000 18:630).

2006-05-26 | E-GEOD-4920 | biostudies-arrayexpress

Genomic and genetic characterization of rice Cen3 reveals evolutionary remnants of a complex centromere (small RNA data)

Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. MPSS was performed to sequence small RNAs that derived from inflorescence and seedling. The method for the MPSS sequencing of small RNAs are described in the paper associated with this dataset (Lu et al., 2005).

2006-05-26 | E-GEOD-4912 | biostudies-arrayexpress

Investigating the effect of Daxx deletion on gene and repeat expression in embryonic stem cells and their differentiated neural derivatives

Project description:Genomes comprise a large fraction of repetitive sequences folded into constitutive heterochromatin to protect genome integrity and cell identity. De novo formation of heterochromatin during preimplantation development is essential to preserve the ground-state of pluripotency and the self-renewal capacity of embryonic stem cells (ESCs). In this study we find that DAXX, an H3.3 chaperone, is essential for ESCs maintenance in the ground-state of pluripotency. DAXX accumulates at pericentromeric regions, and recruits PML and SETDB1, thereby promoting heterochromatin formation. In the absence of DAXX, the 3D-architecture and physical properties of pericentric and peripheral heterochromatin are disrupted, resulting in derepression of major satellite DNA, transposable elements and genes associated with the nuclear lamina. Our data reveal that DAXX is crucial for the maintenance and 3D-organization of the heterochromatin compartment and protects ESCs viability.

2023-09-29 | GSE241701 | GEO

Gene expression from NMuMG cells overexpressing major satellite treated with TGFbeta

Project description:Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of non-coding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here we show that the Snail1 transcription factor represses pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial to mesenchymal transition (EMT), we analyzed the regulation of mouse heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1a, is transiently released from heterochromatin foci in a Snail1/LOXL2–dependent manner during EMT, concomitantly with a down-regulation of major satellite transcription. Global transcriptome analysis indicated that ectopic expression of heterochromatin transcripts affects the transcription profile of EMT-related genes. Additionally, preventing the down-regulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through the histone-modifying enzyme, LOXL2, thus creating the favorable transcriptional state necessary for completing EMT. Keywords: Expression Profiling by array We analyzed 2 arrays from each condition: Control and Major treated 8 hours with TGFbeta

2014-01-01 | E-GEOD-49073 | biostudies-arrayexpress

Genomic and genetic characterization of rice Cen3 reveals evolutionary remnants of a complex centromere (small RNA data)

Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. Keywords: MPSS, small RNA, rice, centromere, Cen3, chromosome 3

2006-05-26 | GSE4912 | GEO

Genomic and genetic characterization of rice Cen3 reveals evolutionary remnants of a complex centromere (mRNA data)

Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. Keywords: MPSS, mRNA, transcriptome, rice, centromere, Cen3, chromosome 3

2006-05-26 | GSE4920 | GEO

CHARACTERIZATION AND DYNAMICS OF MOUSE PERICENTROMERE-ASSOCIATED DOMAINS

Project description:Despite recent progress in genome topology knowledge, the role of repeats, comprising the majority of mammalian genomes, remains elusive. Satellites are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin and aggregate into nuclear chromocenters that are assumed to form a repressive compartment in the nucleus to which genes are recruited for silencing. Here we designed a strategy for genome-wide identification of pericentromere-associated domains (PADs) in different mouse cell types. The ~1000 PADs and non-PADs have similar chromatin states in embryonic stem cells. During lineage commitment however chromocenters progressively overlap with constitutively inactive genomic regions at the nuclear periphery. This suggests that chromocenters do not actively recruit PADs but are themselves attracted to inactive chromatin compartments. However, we also found that experimentally induced proximity of an active locus to chromocenters was sufficient to cause gene repression. Collectively, our data suggests that rather than being a driver of nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions to nuclear compartments where they can contribute to stably maintaining the repressed status of proximal chromosomal regions. We performed satellite 4C (sat4C) on mouse primary thymus tissue, pluripotent mouse embryonic stem cells (ESC) and neural precursor cells (NPC) and terminally differentiated astrocytes (AC) that were sequentially derived from these ESC in vitro

2015-04-01 | E-GEOD-65618 | biostudies-arrayexpress

A transcription factor based mechanism for mouse heterochromatin formation

Project description:We identify Pax3 and Pax9 transcription factors (TFs) as important regulators of mouse heterochromatin. Simultaneous depletion of these factors results in loss of H3K9me3 from Major Satellite repeats and dramatic transcript overexpression. H3K9me3 enrichment at intergenic major satellite repeats is only present if these sequences retain intact Pax and other TF binding sites. H3K9me3 ChIP-seq in mouse ES cells wt and Pax3 KO and Pax3 KO/Pax9 KD

2012-09-16 | E-GEOD-40086 | biostudies-arrayexpress

A transcription factor based mechanism for mouse heterochromatin formation

2012-09-16 | GSE40086 | 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