M6A-eCLIP analysis of mouse BMDM
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE210339 | GEO | 2024/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:N6-methyladenosine (m6A) is the most abundant mRNA modification in mammalian cells, mediated co-transcriptionally by a methyltransferase ‘writer’ complex containing METTL3 as the S-adenosyl methionine (SAM)-binding subunit as well as adaptors such WTAP and ZC3H13
2024-07-01 | GSE210619 | GEO
Project description:N6-methyladenosine (m6A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export and translation. Recent studies discovered m6A methyltransferases (?writer?), demethylases (?eraser?) and binding proteins (?reader?), which modulate m6A methylation. However, the precise m6A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc finger protein, plays an essential role in modulating m6A methylation on polyadenylated RNA in the nucleus. ZC3H13 exists in an evolutionary-conserved macromolecular complex containing WTAP, Virilizer and Hakai. We confirm the interaction among those proteins and demonstrate that knockdown of Zc3h13 in mouse embryonic stem cell (mESC) significantly decreases global m6A level on mRNA, mainly at 3? untranslated regions (3? UTR). Interestingly, fractionation assays show that upon Zc3h13 knockdown a great majority of WTAP, Virilizer and Hakai translocate to the cytoplasm and the nuclear presence of the methyltransferase Mettl3 and Mettl14 also decrease significantly. In contrast, knockdown of WTAP, Virilizer or Hakai does not change the nuclear localization of Zc3h13. This suggests that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6A methylation. Finally, Zc3h13 depletion, as does WTAP, Virilizer or Hakai, impairs self-renewal and triggers mESC differentiation. Taken together, our findings demonstrate that Zc3h13 plays an essential role in anchoring WTAP, Virilizer and Hakai in the nucleus to facilitate m6A methylation and to regulate mESC self-renewal.
2018-03-14 | GSE94148 | GEO
Project description:Epigenetics (DNA methylation) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl
2016-02-02 | GSE74081 | GEO
Project description:Transcriptome (total RNA) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl group for variety of biomolecules such as DNA , histone, RNA, lipids and etc.
2016-02-29 | GSE75430 | GEO
Project description:The SIN3 histone modifying complex regulates the expression of multiple methionine catabolic genes including SAM synthetase (Sam-S) as well as the level of S-adenosyl-methionine (SAM). To further investigate the relationship between methionine catabolism and epigenetic regulation by SIN3, we identified genes controlled by SIN3 and SAM-S. As a global transcriptional regulator, SIN3 impacted a wide range of genes. Independently, SAM-S affected a narrow range of genes. Additional genes, however, were influenced in dual knockdown cells. At some genes, SIN3 and SAM-S act independently, for others, redundantly and for a third set, in opposition. Together, the results obtained in the study of SIN3, a cofactor associated with histone modification, and SAM-S, a metabolic enzyme, uncover a complex relationship on regulating transcription.
2019-11-26 | GSE129145 | GEO
Project description:Reyes-Palomares2012 - a combined model hepatic polyamine and sulfur aminoacid metabolism - version2
Mammalian polyamine metabolism consists of a bi-cycle with two required entrances, omithine and S-adenosyl methionine (SAM), and several alternative exists. The relevant regulatory roles of the short half-life enzymes ornithine decarboxylase (ODC), S-adenosyl methione decarboxylase (SAMDC) and spermindine/spermine acetyl transferase (SSAT) in polyamine metabolism are well studied, and has been modelled here.
This model is described in the article:
A combined model of hepatic polyamine and sulfur amino acid metabolism to analyze S-adenosyl methionine availability.
Reyes-Palomares A, Montañez R, Sánchez-Jiménez F, Medina MA
Amino Acids, February 2012, Volume 42, Issue 2-3, pp 597-610
Abstract:
Many molecular details remain to be uncovered concerning the regulation of polyamine metabolism. A previous model of mammalian polyamine metabolism showed that S-adenosyl methionine availability could play a key role in polyamine homeostasis. To get a deeper insight in this prediction, we have built a combined model by integration of the previously published polyamine model and one-carbon and glutathione metabolism model, published by different research groups. The combined model is robust and it is able to achieve physiological steady-state values, as well as to reproduce the predictions of the individual models. Furthermore, a transition between two versions of our model with new regulatory factors added properly simulates the switch in methionine adenosyl transferase isozymes occurring when the liver enters in proliferative conditions. The combined model is useful to support the previous prediction on the role of S-adenosyl methionine availability in polyamine homeostasis. Furthermore, it could be easily adapted to get deeper insights on the connections of polyamines with energy metabolism.
Notes by the author:
This model combines BIOMD0000000190 and BIOMD0000000268 from BioModels Database, both models include corrections respect to their originals publications.
To simulate a MATI/MATIII switch to MATII in proliferating liver:
We set to 0 the Vmax parameters of MATI and MATIII
We included MATII reaction equation.
We add a regulation factor dependent of SAM levels in ODC and SAMDCe rates of synthesis (66.5/[SAM]).
H2O2 was increased in a 50 % according to an initial state ofproliferating and regenerating liver.
This model is hosted on BioModels Database
and identified
by: MODEL1305060001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000450 | BioModels
Project description:label the cells overexpressed Myc tagged METTL3 and Flag tagged WTAP with 4-SU, the RNA bound by METT3,WTAP can be got by Myc or Flag IP followed by RNA isolation by using the TRIzol (Invitrogen) reagent by following the company manual.the RNA was then used for library preparation using a TruSeq™ RNA Sample Prep Kit v2 (Illumina, San Diego, CA, USA) according to the manufacturer’s protocol.The libraries were sequenced using HiSeq2000 (Illumina) in single-read mode, creating reads with a length of 50 bp. Sequencing chemistry v2 (Illumina) was used and samples were multiplexed in two samples per lane. discovery of the binding motif of METTL3，WTAP in METTL3，WTAP overexpressed Human 293T cells
2014-01-16 | E-GEOD-50580 | biostudies-arrayexpress
Project description:Transcriptome (total RNA) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl group for variety of biomolecules such as DNA , histone, RNA, lipids and etc. Two-condition experiment, bovine non-treated expanded blastocysts (pools of 10) vs bovine SAM-treated expanded blastocysts. Four biological replicates of each tissue were hybridized to four two-color arrays in a dye-balanced design.
2016-02-29 | E-GEOD-75430 | biostudies-arrayexpress
Project description:Using a genome-scale CRISPR knockout screening in mouse embryonic stem cells, we identify m6A RNA methylation as an important regulatory component that restricts the activity of endogenous retroviruses of the IAP (intracisternal A-particles) family. The m6A methylation of IAP mRNAs occurs on their 5’ end, is catalyzed by the complex of methyltransferase-like (METTL)3/METTL14 proteins whose depletion, along with other complex subunits, namely WTAP and ZC3H13, leads to increased IAP transcript abundance. Using auxin-dependent degron, we show that rapid removal of METTL3, METTL14 and ZC3H13 further increases IAP RNA abundance in a progressive and reversible fashion. Finally, we demonstrate that m6A RNA reduces the stability of IAP transcripts
2020-08-11 | GSE156007 | GEO
Project description:Using a genome-scale CRISPR knockout screening in mouse embryonic stem cells, we identify m6A RNA methylation as an important regulatory component that restricts the activity of endogenous retroviruses of the IAP (intracisternal A-particles) family. The m6A methylation of IAP mRNAs occurs on their 5’ end, is catalyzed by the complex of methyltransferase-like (METTL)3/METTL14 proteins whose depletion, along with other complex subunits, namely WTAP and ZC3H13, leads to increased IAP transcript abundance. Using auxin-dependent degron, we show that rapid removal of METTL3, METTL14 and ZC3H13 further increases IAP RNA abundance in a progressive and reversible fashion. Finally, we demonstrate that m6A RNA reduces the stability of IAP transcripts
2020-04-13 | GSE145315 | GEO