MRG proteins are shared by multiple protein complexes with distinct functions.
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ABSTRACT:
PROVIDER: PRJNA752373 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we characterized MORF4L1/MRG15 interactome. Using Flag-ChIP-sequencin K562 cells, we first claimed that both MRG15 isoforms (long or short chromodomain) and MORF4L2/MRGX which does not contain any chromodomain, shared mostly the same targets. Then, we described a new factor associated to MRG15, called EP400NL. EP400NL binds to BRD8 also linked to MRGBP and MRG15/X to form a new complex homolog to the yeast TINTIN. Using RNA-sequencing in BRD8 or MRGBP or MRG15/MRGX and KAT5/TIP60-depleted U2OS cells, we observed that human TINTIN plays a role in gene expression regulation independently of NuA4/TIP60 complex.
2021-08-17 | GSE181533 | GEO
Project description: Not available
| S-EPMC9253478 | biostudies-literature
Project description:- Human TINTIN complex is composed of BRD8/MRGBP/MRG15 or MRGX and a new subunit EP400NL.
- Purification of endogenous EP400NL.
- Human TINTIN regulated gene expression.
- W172A Y235A MRG15 disturbs PALB2 interactions.
- W78A F105A MRGBP inhibits the interaction with MRG15.
2022-05-24 | MSV000089533 | MassIVE
Project description:We compared wild type N2 to mrg-1 mutants L1 larvae. Genes tend to be upregulated rather than downregulated in these mutants. Comparison to available ChIPseq datasets indicates that the upregulated genes are heterochromatic and are not enriched for H3K36 methylation, indicating that MRG-1 loss derepresses heterochromatin indirectly.
2019-04-11 | GSE115998 | GEO
Project description:BACKGROUND: Preclinical studies have demonstrated that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a combination of plerixafor and low-dose tacrolimus (MRG-001) improves wound healing, promotes tissue regeneration and prevents allograft rejection. This first‐in‐human phase I dose‐escalation study evaluates the safety, tolerability, pharmacokinetics and pharmacodynamics of MRG-001, a novel fixed-dose combination drug. METHODS: In this Phase 1, double‐blind, randomized, placebo-controlled study, multiple ascending dose (MAD) cohorts are randomized to receive MRG-001 containing up to 0.02 mL/kg (plerixafor 24 mg/mL and tacrolimus 0.5 mg/mL) or saline placebo, subcutaneously every other day (SC, QAD) for 5 days (ClinicalTrials.gov: NCT04646603)The primary outcome is safety and tolerability. Safety and functional assessments are performed throughout the study. Blood samples are collected to evaluate systemic exposure. Fluorescence-activated cell sorting analysis and RNA expression of peripheral blood mononuclear cells (PBMCs) are used to evaluate the pharmacodynamics. RESULTS: Fourteen subjects received MRG-001 and 7 received a placebo. MRG-001 is safe and well-tolerated over the selected dose range. No deaths or severe adverse events are reported. There are no clinically significant laboratory changes after MRG-001 administration, apart from the predicted generalized leukocytosis. The intermediate dose group (0.01 mL/kg) showed the most significant white blood cell mobilization over time and increased by 2-4 fold from baseline and returned to baseline levels prior to the next injection. Circulating immune cells including FOXP3+ regulatory T cells and hematopoietic stem cells (CD45IntCD34+) increased significantly after MRG-001 injection. PBMC RNA sequencing and gene set enrichment analysis revealeds 31 down-regulated pathways in the intermediate dose MRG-001 group compared to no changes in the placebo group. CONCLUSION: MRG-001 is safe and well-tolerated across the full dose ranges tested. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration. A Phase II trial to treat severely and critically ill COVID-19 patients with MRG-001 has been initiated (NCT04646603) and a second phase II trial will explore the potential of MRG-001 to accelerate wound healing (NCT05844527),
2023-07-24 | GSE237965 | GEO
Project description:Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions
| PRJNA475784 | ENA
Project description:Transcriptomic profiling identifies unique and shared functions of oncogenic KRAS and RIT1
| PRJNA610636 | ENA
Project description:Abstract: Chromatin-regulating factors safeguard cell identities by suppressing ectopic gene expression thereby imposing barriers for transcription factor-induced reprogramming of cell fates. Identifying factors opposing the induction of ectopic cell fates is important to better understand developmental differentiation processes and may improve cellular reprogramming for therapeutic approaches. Reprogramming barriers have previously been studied mostly in tissue cultures. Hence, knowledge about chromatin regulators acting as reprogramming barriers in vivo needs improvement. We therefore made use of the nematode C. elegans as an in vivo gene discovery tool and interrogated its chromatin-regulating factors for being involved in protecting germ cells against reprogramming to neurons by performing automated RNAi screening. We identified the conserved chromodomain factor MRG-1 (MRG15 in humans) as a barrier for converting germ cells into neurons and characterized its protein-protein and genome interactions using IP-MS and ChIP-seq in wild-type animals versus mutants lacking the germline. We found that MRG-1 associates predominantly with genes carrying active histone modifications but it also cooperates with the histone H3K9 methyltransferase SET-26 in order to prevent conversion of germ cells into neurons. Conserved chromatin regulators such as MRG-1 potentially have similar functions in higher organisms as shown previously for the histone chaperone LIN-53 (CAF-1p48/RBBP7). LIN-53 was initially identified as a barrier of C. elegans germ cell reprogramming and was later shown to also block reprogramming in mammals. Such remarkable conservation of reprogramming barriers illustrates that understanding cell fate protection in C. elegans could help to improve the generation of new cell types for therapeutic approaches in humans.
2019-02-21 | GSE110969 | GEO
Project description:Unique and Shared Roles for Histone H3K36 Methylation States in Transcription Regulation Functions
| PRJNA517160 | ENA
Project description:Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, and DNA repair. However, it was not known whether the different methylation states of H3K36 have distinct biological functions. Here, we use engineered forms of Set2 that produce different lysine methylation states to identify unique and shared functions for H3K36 modifications. Although H3K36me1/2 and H3K36me3 are functionally redundant in many SET2 deletion phenotypes, we found that H3K36me3 has a unique function related to Bur1 kinase activity and FACT (facilitates chromatin transcription) complex function. Further, during nutrient stress, either H3K36me1/2 or H3K36me3 represses high levels of histone acetylation and cryptic transcription that arises from within genes. Our findings uncover the potential for the regulation of diverse chromatin functions by different H3K36 methylation states.
2020-04-29 | GSE125684 | GEO