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Article ; Online: Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes.

Barata, Tânia / Duarte, Isabel / Futschik, Matthias E

2023 Volume 14, Issue 3

Abstract: Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes ... ...

Abstract	Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and ageing. To decipher their underlying genetic substrate, it is important to identify so-called stemness genes that are common to different stem cell types and are consistently identified across different studies. In this meta-analysis, 21 individual stemness signatures for humans and another 21 for mice, obtained from a variety of stem cell types and experimental techniques, were compared. Although we observed biological and experimental variability, a highly significant overlap between gene signatures was identified. This enabled us to define integrated stemness signatures (ISSs) comprised of genes frequently occurring among individual stemness signatures. Such integrated signatures help to exclude false positives that can compromise individual studies and can provide a more robust basis for investigation. To gain further insights into the relevance of ISSs, their genes were functionally annotated and connected within a molecular interaction network. Most importantly, the present analysis points to the potential roles of several less well-studied genes in stemness and thus provides promising candidates for further experimental validation.
MeSH term(s)	Humans ; Animals ; Mice ; Stem Cells
Language	English
Publishing date	2023-03-18
Publishing country	Switzerland
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030745
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Article ; Online: Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

Barata, Tânia / Duarte, Isabel / Futschik, Matthias E.

Genes (Basel). 2023 Mar. 18, v. 14, no. 3

2023

Abstract	Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and ageing. To decipher their underlying genetic substrate, it is important to identify so-called stemness genes that are common to different stem cell types and are consistently identified across different studies. In this meta-analysis, 21 individual stemness signatures for humans and another 21 for mice, obtained from a variety of stem cell types and experimental techniques, were compared. Although we observed biological and experimental variability, a highly significant overlap between gene signatures was identified. This enabled us to define integrated stemness signatures (ISSs) comprised of genes frequently occurring among individual stemness signatures. Such integrated signatures help to exclude false positives that can compromise individual studies and can provide a more robust basis for investigation. To gain further insights into the relevance of ISSs, their genes were functionally annotated and connected within a molecular interaction network. Most importantly, the present analysis points to the potential roles of several less well-studied genes in stemness and thus provides promising candidates for further experimental validation.
Keywords	genes ; meta-analysis ; stem cells
Language	English
Dates of publication	2023-0318
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030745
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Article ; Online: Detection of Novel Potential Regulators of Stem Cell Differentiation and Cardiogenesis through Combined Genome-Wide Profiling of Protein-Coding Transcripts and microRNAs.

Machado, Rui / Sachinidis, Agapios / Futschik, Matthias E

Cells

2021 Volume 10, Issue 9

Abstract: In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation ... ...

Abstract	In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the in vivo system remains unclear. In this study, we profiled simultaneous genome-wide measurements of mRNAs and microRNAs (miRNAs) of differentiating murine ESCs (mESCs) and integrated putative miRNA-gene interactions to assess miRNA-driven gene regulation. To identify interactions conserved between in vivo and in vitro, we combined our analysis with a recent transcriptomic study of early murine heart development in vivo. We detected over 200 putative miRNA-mRNA interactions with conserved expression patterns that were indicative of gene regulation across the in vitro and in vivo studies. A substantial proportion of candidate interactions have been already linked to cardiogenesis, supporting the validity of our approach. Notably, we also detected miRNAs with expression patterns that closely resembled those of key developmental transcription factors. The approach taken in this study enabled the identification of miRNA interactions in in vitro models with potential relevance for early cardiogenic development. Such comparative approaches will be important for the faithful application of stem cells in cardiovascular research.
MeSH term(s)	Animals ; Cell Differentiation ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Exons ; Gene Expression Profiling ; Genome-Wide Association Study ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Organogenesis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome ; Whole Exome Sequencing
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2021-09-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092477
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Article ; Online: CCBE1 Is Essential for Epicardial Function during Myocardium Development.

Bonet, Fernando / Añez, Sabrina Brito / Inácio, José Manuel / Futschik, Matthias E / Belo, José Antonio

International journal of molecular sciences

2022 Volume 23, Issue 20

Abstract: The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the ... ...

Abstract	The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a
MeSH term(s)	Mice ; Animals ; Heart/physiology ; Organogenesis ; Pericardium/metabolism ; Myocardium/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Mice, Knockout ; Collagen/metabolism
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232012642
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Article ; Online: Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.

Diaz, Laura R / Gil-Ranedo, Jon / Jaworek, Karolina J / Nsek, Nsikan / Marques, Joao Pinheiro / Costa, Eleni / Hilton, David A / Bieluczyk, Hubert / Warrington, Oliver / Hanemann, C Oliver / Futschik, Matthias E / Bossing, Torsten / Barros, Claudia S

EMBO reports

2024 Volume 25, Issue 1, Page(s) 168–197

Abstract: Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain ...

Abstract	Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.
MeSH term(s)	Animals ; Humans ; Brain/metabolism ; Brain Neoplasms/metabolism ; Carcinogenesis/pathology ; Cell Transformation, Neoplastic/pathology ; DNA-Binding Proteins/metabolism ; Drosophila/genetics ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Glioblastoma/metabolism ; Glioma/pathology ; Minor Histocompatibility Antigens/metabolism ; Neoplastic Stem Cells/metabolism ; RNA-Binding Proteins/metabolism ; Proto-Oncogene Proteins c-myc/metabolism
Chemical Substances	DNA-Binding Proteins ; Drosophila Proteins ; HEATR1 protein, human ; Minor Histocompatibility Antigens ; RNA-Binding Proteins ; MYC protein, human ; Proto-Oncogene Proteins c-myc
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.1038/s44319-023-00017-1
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Genome-wide identification and characterization of Fur-binding sites in the cyanobacteria Synechocystis sp. PCC 6803 and PCC 6714.

Riediger, Matthias / Hernández-Prieto, Miguel A / Song, Kuo / Hess, Wolfgang R / Futschik, Matthias E

DNA research : an international journal for rapid publication of reports on genes and genomes

2021 Volume 28, Issue 6

Abstract: The Ferric uptake regulator (Fur) is crucial to both pathogenic and non-pathogenic bacteria for the maintenance of iron homeostasis as well as the defence against reactive oxygen species. Based on datasets from the genome-wide mapping of transcriptional ... ...

Abstract	The Ferric uptake regulator (Fur) is crucial to both pathogenic and non-pathogenic bacteria for the maintenance of iron homeostasis as well as the defence against reactive oxygen species. Based on datasets from the genome-wide mapping of transcriptional start sites and transcriptome data, we identified a high confidence regulon controlled by Fur for the model cyanobacterium Synechocystis sp. PCC 6803 and its close relative, strain 6714, based on the conserved strong iron starvation response and Fur-binding site occurrence. This regulon comprises 33 protein-coding genes and the sRNA IsaR1 that are under the control of 16 or 14 individual promoters in strains 6803 and 6714, respectively. The associated gene functions are mostly restricted to transporters and enzymes involved in the uptake and storage of iron ions, with few exceptions or unknown functional relevance. Within the isiABC operon, we identified a previously neglected gene encoding a small cysteine-rich protein, which we suggest calling, IsiE. The regulation of iron uptake, storage, and utilization ultimately results from the interplay between the Fur regulon, several other transcription factors, the FtsH3 protease, and the sRNA IsaR1.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Binding Sites ; Gene Expression Regulation, Bacterial ; Regulon ; Synechocystis/genetics ; Synechocystis/metabolism
Chemical Substances	Bacterial Proteins
Language	English
Publishing date	2021-10-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1212508-8
ISSN	1756-1663 ; 1340-2838
ISSN (online)	1756-1663
ISSN	1340-2838
DOI	10.1093/dnares/dsab023
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Zs.A 4123: Show issues

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Article ; Online: Rapid antigen testing for SARS-CoV-2 by lateral flow assay: A field evaluation of self- and professional testing at UK community testing sites.

Futschik, Matthias E / Johnson, Samuel / Turek, Elena / Chapman, David / Carr, Simon / Thorlu-Bangura, Zareen / Klapper, Paul E / Sudhanva, Malur / Dodgson, Andrew / Cole-Hamilton, Joanna R / Germanacos, Nick / Kulasegaran-Shylini, Raghavendran / Blandford, Edward / Tunkel, Sarah / Peto, Timothy / Hopkins, Susan / Fowler, Tom

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

2024 Volume 171, Page(s) 105654

Abstract: Background: The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to ... ...

Abstract	Background: The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning. Methods: Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling. Results: 16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR. Conclusions: Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations.
MeSH term(s)	Humans ; COVID-19/diagnosis ; Prospective Studies ; SARS-CoV-2 ; Immunologic Tests ; United Kingdom ; Sensitivity and Specificity
Language	English
Publishing date	2024-02-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1446080-4
ISSN	1873-5967 ; 1386-6532
ISSN (online)	1873-5967
ISSN	1386-6532
DOI	10.1016/j.jcv.2024.105654
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Zs.A 3790: Show issues

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Article ; Online: Faster detection of asymptomatic COVID-19 cases among care home staff in England through the combination of SARS-CoV-2 testing technologies.

Ryan, Finola / Cole-Hamilton, Joanna / Dandamudi, Niharika / Futschik, Matthias E / Needham, Alexander / Saquib, Rida / Kulasegaran-Shylini, Raghavendran / Blandford, Edward / Kidd, Michael / O'Moore, Éamonn / Hall, Ian / Sudhanva, Malur / Klapper, Paul / Dodgson, Andrew / Moore, Adam / Duke, Madeleine / Tunkel, Sarah / Kenny, Chris / Fowler, Tom

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7475

Abstract: To detect SARS-CoV-2 amongst asymptomatic care home staff in England, a dual-technology weekly testing regime was introduced on 23 December 2020. A lateral flow device (LFD) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) test ... ...

Abstract	To detect SARS-CoV-2 amongst asymptomatic care home staff in England, a dual-technology weekly testing regime was introduced on 23 December 2020. A lateral flow device (LFD) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) test were taken on the same day (day 0) and a midweek LFD test was taken three to four days later. We evaluated the effectiveness of using dual-technology to detect SARS-CoV-2 between December 2020 to April 2021. Viral concentrations derived from qRT-PCR were used to determine the probable stage of infection and likely level of infectiousness. Day 0 PCR detected 1,493 cases of COVID-19, of which 53% were in the early stages of infection with little to no risk of transmission. Day 0 LFD detected 83% of cases that were highly likely to be infectious. On average, LFD results were received 46.3 h earlier than PCR, enabling removal of likely infectious staff from the workplace quicker than by weekly PCR alone. Demonstrating the rapidity of LFDs to detect highly infectious cases could be combined with the ability of PCR to detect cases in the very early stages of infection. In practice, asymptomatic care home staff were removed from the workplace earlier, breaking potential chains of transmission.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19 Testing ; England/epidemiology
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-57817-1
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Article ; Online: PCR testing of traced contacts for SARS-CoV-2 in England, January to July 2021.

Nonnenmacher, Toby / Dandamudi, Niharika / Futschik, Matthias Erwin / Tunkel, Sarah A / Kulasegaran-Shylini, Raghavendran / Germanacos, Nick / Cole-Hamilton, Joanna / Blandford, Edward / Goddard, Ashley / Hillier, Joe / Finer, Stephen / Hopkins, Susan / Fowler, Tom

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

2023 Volume 28, Issue 44

Abstract: BackgroundThe NHS Test and Trace (NHSTT) programme was established in May 2020 in England to deliver SARS-CoV-2 testing and contact tracing in order to identify infected individuals and reduce COVID-19 spread. To further control transmission, people ... ...

Abstract	BackgroundThe NHS Test and Trace (NHSTT) programme was established in May 2020 in England to deliver SARS-CoV-2 testing and contact tracing in order to identify infected individuals and reduce COVID-19 spread. To further control transmission, people identified as contacts were asked to self-isolate for 10 days and test only if they became symptomatic. From March 2021, eligibility criteria for PCR testing expanded to include asymptomatic contacts of confirmed cases.AimTo analyse testing patterns of contacts before and after the change in testing guidance in England to assess the impact on PCR testing behaviour with respect to symptom status and contact type.MethodsTesting and contact tracing data were extracted from the national data systems and linked. Subsequently, descriptive statistical analysis was applied to identify trends in testing behaviour.ResultsBetween 1 January and 31 July 2021, over 5 million contacts were identified and reached by contact tracers; 42.3% took a PCR test around the time they were traced. Overall positivity rate was 44.3% and consistently higher in symptomatic (60-70%) than asymptomatic (around 20%, March-June) contacts. The proportion of tests taken by asymptomatic contacts increased over time, especially after the change in testing guidance. No link was observed between uptake of PCR tests and vaccination coverage. Fully vaccinated contacts showed lower positivity (23.8%) than those with one dose (37.2%) or unvaccinated (51.0%).ConclusionAlmost 1 million asymptomatic contacts were tested for SARS-CoV-2, identifying 214,056 positive cases, demonstrating the value of offering PCR testing to this group.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19 Testing ; COVID-19/diagnosis ; COVID-19/epidemiology ; Polymerase Chain Reaction ; England/epidemiology
Language	English
Publishing date	2023-11-02
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	1338803-4
ISSN	1560-7917 ; 1025-496X
ISSN (online)	1560-7917
ISSN	1025-496X
DOI	10.2807/1560-7917.ES.2023.28.44.2300019
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Zs.A 5066: Show issues

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Article ; Online: Loss of H3K9 trimethylation alters chromosome compaction and transcription factor retention during mitosis.

Djeghloul, Dounia / Dimond, Andrew / Cheriyamkunnel, Sherry / Kramer, Holger / Patel, Bhavik / Brown, Karen / Montoya, Alex / Whilding, Chad / Wang, Yi-Fang / Futschik, Matthias E / Veland, Nicolas / Montavon, Thomas / Jenuwein, Thomas / Merkenschlager, Matthias / Fisher, Amanda G

Nature structural & molecular biology

2023 Volume 30, Issue 4, Page(s) 489–501

Abstract: Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we ... ...

Abstract	Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we show that enzymes that catalyze H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly, however, mutants lacking histone 3 lysine 9 trimethylation (H3K9me3) have unusually small and compact mitotic chromosomes associated with increased histone H3 phospho Ser10 (H3S10ph) and H3K27me3 levels. Chromosome size and centromere compaction in these mutants were rescued by providing exogenous first protein lysine methyltransferase Suv39h1 or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wild-type versus Suv39h1/Suv39h2 double-null mouse embryonic stem cells revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.
MeSH term(s)	Animals ; Mice ; Transcription Factors/metabolism ; Proteomics ; Histones/metabolism ; Heterochromatin ; DNA Methylation ; Mitosis ; Polycomb-Group Proteins/genetics ; Methyltransferases/metabolism
Chemical Substances	Transcription Factors ; Histones ; Heterochromatin ; Polycomb-Group Proteins ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-023-00943-7
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