Ladder-like multimerization of FoxP3 enables microsatellite recognition and DNA bridging
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1018994 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24624490_1.fastq.gz | Fastqsanger.gz | |||
| SRR24624490_2.fastq.gz | Fastqsanger.gz | |||
| SRR24624491_1.fastq.gz | Fastqsanger.gz | |||
| SRR24624491_2.fastq.gz | Fastqsanger.gz | |||
| SRR24624492_1.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-09 | GSE243606 | GEO
Project description:To investigate the impact of FoxP3 multimerization mutants on FoxP3's genome-wide gene expression profiles, we conducted FoxP3 RNA-seq experiments using mouse CD4+ T cells. The results indicated that all of these multimerization mutants had an effect on FoxP3 gene expression profiles, including some well-established Treg signatures.
2023-10-09 | GSE243602 | GEO
Project description:FoxP3, an essential transcription factor for regulatory T cells (Tregs), forms higher-order multimers on TnG microsatellites in the genome. Although a previous study has shown that FoxP3 can form head-to-head (H-H) dimers on inverted repeats of forkhead motifs (IR-FKHM), in vivo evidence for this configuration was elusive. An unbiased FoxP3 pull-down sequencing approach identified a wide range of sequences supporting H-H dimerization, enabling systematic genomic analysis. This work revealed that FoxP3 binds DNA in Tregs as both H-H dimers and higher-order multimers, often incorporating one half-site of the H-H dimer into TnG repeats. A robust H-H interaction can seed multimerization on adjacent TnG repeats, enhancing assembly even on suboptimal sequences. Unlike other FoxP transcription factors, H-H dimerization is unique to FoxP3. Chimeric construct analyses identified a loop adjacent to the forkhead domain as the determinant for this distinctive function, underscoring a unique synergism between two binding modes.
2025-10-31 | GSE294472 | GEO
Project description:To investigate the impact of FoxP3 multimerization mutants on FoxP3's genome-wide DNA binding, with a particular focus on TnG-repeats binding, we conducted FoxP3 ChIP-seq experiments using mouse CD4+ T cells. The results revealed that all of these multimerization mutants have the potential to influence FoxP3 DNA binding, including its interaction with TnG-repeats.
2023-10-09 | GSE243599 | GEO
Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia. Epididymal adipose tissue from wild type and XBP1-overexpressing mice was subjected to gene expression profiling.
2013-11-21 | E-GEOD-36031 | biostudies-arrayexpress
Project description:Cooperativity between head-to-head dimerization and head-to-tail multimerization of FoxP3 transcription factor
| PRJNA1249512 | ENA
Project description:In Saccharomyces cerevisiae, the SAGA complex regulates its own activity by undergoing multimerization. This multimerization is triggered by SAGA autoacetylation at three sites on its Ada3 subunit, allowing recognition of this acetylation by the bromodomain of the Gcn5/Spt7 SAGA subunit. Once multimerized, SAGA is capable of cooperatively acetylating chromatin, and an inability to autoacetylate Ada3 leads to transcriptional and phenotypic defects in a wide range of stress-activated genes. The SAGA multimerization increased significantly in media with Sucorse as the only carbon resource than that with Glucose. In this study, the high-throughput sequence of wild type (WT) strain, Ada3 acetylation mutant (Ada3-3KR), Gcn5 bromodomain mutant (Gcn5m) and Spt7 bromodomain mutant (Spt7m) indicate a new function for Ada3 acetylation, show which genes transcription can be regulated by SAGA multimers.
2021-11-29 | GSE161887 | GEO
Project description:The physiological role of the spliced form of X-box-binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. Here we show that overexpression of XBP1s promotes adiponectin multimerization in adipocytes, thereby regulating systemic glucose homeostasis. Ectopic expression of XBP1s in adipocytes improves glucose tolerance and insulin sensitivity in both lean and obese (ob/ob) mice. The beneficial effect of adipocyte XBP1s on glucose homeostasis is associated with elevated serum levels of HMW adiponectin and indeed, is adiponectin dependent. Mechanistically, XBP1s promotes adiponectin multimerization rather than activating its transcription likely through a direct regulation of the expression of several ER-chaperones involved in adiponectin maturation, including Grp78, Pdia6, ERp44 and DsbA-L. Thus, we conclude that XBP1s is an important regulator of adiponectin multimerization, which may lead to a new therapeutic approach for the treatment of type 2 diabetes and hypoadiponectinemia.
2013-11-21 | GSE36031 | GEO
Project description:Oncoproteins of the MYC family drive the development of numerous human tumors. In unperturbed cells, MYC proteins bind to virtually all active promoters and control transcription by RNA Polymerase II (RNAPII). MYC proteins can also coordinate transcription with DNA replication and promote the repair of transcription-associated DNA damage, but how they exert these mechanistically diverse functions is unknown. Here we show that MYC dissociates from many of its binding sites in active promoters and forms multimeric, often sphere-like structures in response to perturbation of transcription elongation, mRNA splicing or inhibition of the proteasome. Multimerization is accompanied by a global change in the MYC interactome towards proteins involved in transcription termination and RNA processing. MYC multimers accumulate on chromatin immediately adjacent to stalled replication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks. MYC multimerization is triggered in a HUWE1 and ubiquitylation-dependent manner. At active promoters, MYC multimers block antisense transcription and stabilize FANCD2 association with chromatin. This limits DNA double-strand break formation during S-phase and allows rapid recovery from replication stress, suggesting that multimerization of MYC enables tumor cells to proliferate under stressful conditions
2022-09-07 | GSE210163 | GEO
Project description:Regulatory T cells have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and in addition the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. ATP was secreted by both T effector and regulatory T cells and was reduced by mitochondrial respiration inhibitors. Thus Foxp3 imparts a selective advantage in ATP generation capacity to the cell and may exploit this as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a comparative quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing T cells and Foxp3 positive iTreg and Foxp3 negative activated CD4 T cells in addition to human peripheral blood natural Treg. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 drives a significant up regulation of several members of the mitochondrial electron transport chain.
2017-02-15 | PXD001789 | Pride