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ChIP-seq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

ABSTRACT: ChIP-seq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

PROVIDER: PRJNA575035 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10207274_1.fastq.gz	Fastqsanger.gz
	SRR10207274_2.fastq.gz	Fastqsanger.gz
	SRR10207275_1.fastq.gz	Fastqsanger.gz
	SRR10207275_2.fastq.gz	Fastqsanger.gz
	SRR10207276_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

RNAseq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

Project description:Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a human THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often due to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.

2019-12-20 | GSE138207 | GEO

ChIP-seq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

2019-12-20 | GSE138205 | GEO

RNAseq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

Project description:RNAseq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

| PRJNA575036 | ENA

THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation

Project description:THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation

| PRJNA575034 | ENA

THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation.

Project description:Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often owing to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin (vitamin B12) metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.

| S-EPMC6944463 | biostudies-literature

THAP11 mutations in a patient with a cblX-like phenotype implicates THAP11 in the regulation of cobalamin metabolism and early vertebrate development

Project description:Mutations in HCFC1 are associated with cblX (MIM309541), an X-linked recessive disorder, characterized by defects in cobalamin metabolism and other developmental defects. HCFC1 is a transcriptional co-regulator, which interacts with transcription factors to regulate the expression of a myriad of genes. Notably, HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. In addition, the HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutations in THAP11 may also result in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with phenotypic features that overlap cblX, but did not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant in THAP11, c.240C>G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo, demonstrate that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. Further, the loss of THAP11 in zebrafish embryos, results in craniofacial abnormalities including the complete loss of Meckel’s cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work which demonstrated a role for HCFC1 in vertebrate craniofacial development. Furthermore, our high throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11 that likely contribute to the phenotypes associated with cblX and related disorders. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development.

| EGAS00001002201 | EGA

THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-20 | GSE138208 | GEO

RNA-seq of mouse embryonic stem cells with Ronin/Thap11 knockout

Project description:RNA-seq of Ronin/Thap11 knockout and heterozygous control mouse ES cells to assess the role of Ronin

2022-01-31 | E-MTAB-10024 | biostudies-arrayexpress

Comparative proteomics of cobalamin-dependent propionate production by the rumen bacterium Xylanibacter ruminicola

Project description:Xylanibacter ruminicola is an abundant rumen bacterium that produces propionate in a cobalamin-dependent manner. However, the effect of cobalamin supplementation on the expression of propionate pathway enzymes has yet to be investigated. To assess this, comparative transcriptomics and proteomics was carried out on X. ruminicola KHP1 cultures grown in defined media in the presence and absence of cobalamin. Cobalamin supplementation did not affect expression of most propionate pathway proteins, with the only differentially abundant pathway enzyme being the cobalamin-dependent methylmalonyl-CoA mutase, which showed a minor upregulation in the presence of cobalamin. Our results demonstrate expression of the propionate pathway regardless of cobalamin availability, suggesting that cobalamin-dependent induction of propionate production by X. ruminicola is controlled post-translationally.

2024-10-14 | PXD053273 | Pride

Inherited disorders of cobalamin metabolism disrupt nucleocytoplasmic transport of mRNA through impaired methylation/phosphorylation of HuR

Project description:Molecular mechanisms underlying the neurological disorders of inherited diseases of cobalamin metabolism remain obscure. Transcriptome data from a cell model with impaired cobalamin metabolism implicated dysregulated RNA metabolism and endoplasmic reticulum stress. Evidence from the cell model, Cd320 knockout mice, and fibroblasts with inborn errors of cobalamin metabolism indeed supported the findings of transcriptome. These models allowed the demonstration of RNA binding proteins (RBP) mislocalized subcellularly due to failed nucleocytoplasmic shuttling. In the case of HuR, decreased RBP interaction with nuclear receptor CRM1/exportin accounted for the failure, and HuR hypomethylation and dephosphorylation were the causes of this. Our evidence further indicated that decreased SAM and CARM1 level and increased PP2A expression were partly responsible for the post translational modifications of HuR. The consequent HuR mislocalization to the nucleus in turn reduced the expression of SIRT1 and other genes involved in brain development, neuroplasticity, myelin formation, and brain aging. This mislocalization was reversible upon treatment with siPpp2ca, cobalamin, S-adenosylmethionine, or PP2A inhibitor okadaic acid. In conclusion, our data highlight the key roles of cobalamin metabolism on HuR-mediated mRNA stability, which when disrupted produce genomic changes consistent with the effects of inborn errors of cobalamin on brain development, neuroplasticity and myelin formation.

2018-07-20 | GSE103417 | GEO

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