Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The human AlkB homologue 4 interacts with proteins associated with transcription (expression)

ABSTRACT: The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologues (ALKBH1-8 and FTO). ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologues are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state and support the previous association of ALKBH7 with spermatogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39127 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA170065

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The human AlkB homologue 4 interacts with proteins associated with transcription (expression)

Project description:The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologues (ALKBH1-8 and FTO). ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologues are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state and support the previous association of ALKBH7 with spermatogenesis. Gene expression profiling of ALKBH4 and ALKBH7 over-expression

2013-12-01 | E-GEOD-39127 | biostudies-arrayexpress

The human AlkB homologue 4 interacts with proteins associated with transcription (methylation)

Project description:The Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from E. coli is a demethylase which repairs alkyl lesions in DNA, as well as RNA, through a direct reversal mechanism. Humans possess nine AlkB homologues (ALKBH1-8 and FTO). ALKBH2 and ALKBH3 display demethylase activities corresponding to that of AlkB, and both ALKBH8 and FTO are RNA modification enzymes. The biochemical functions of the rest of the homologues are still unknown. To increase our knowledge on the functions of ALKBH4 and ALKBH7 we have here performed yeast two-hybrid screens to identify interaction partners of the two proteins. While no high-confidence hits were detected in the case of ALKBH7, several proteins associated with chromatin and/or involved in transcription were found to interact with ALKBH4. For all interaction partners, the regions mediating binding to ALKBH4 comprised domains previously reported to be involved in interaction with DNA or chromatin. Furthermore, some of these partners showed nuclear co-localization with ALKBH4. However, the global gene expression pattern was only marginally altered upon ALKBH4 over-expression, and larger effects were observed in the case of ALKBH7. Although the molecular function of both proteins remains to be revealed, our findings suggest a role for ALKBH4 in regulation of gene expression or chromatin state and support the previous association of ALKBH7 with spermatogenesis. Comparison of DNA methylation patterns in cells over expressing ALKBH4 and ALKBH7

2013-12-01 | E-GEOD-39126 | biostudies-arrayexpress

The human AlkB homologue 4 interacts with proteins associated with transcription (methylation)

2013-12-01 | GSE39126 | GEO

ALKBH8 suppresses oxidative stress and ameliorates inflammation via blocking NFκB/NLRP3 axis in Sepsis

Project description:The molecular mechanisms underlying sepsis pathogenesis and its regulation are incompletely understood. Here we demonstrated that human AlkB homologue, ALKBH8, plays a critical role in sepsis. we demonstrated that inhibition of Reactive oxygen species (ROS) production by using N-acetylcysteine (NAC) antagonized the effect of ALKBH8 knockdown on inflammation response and NFκB/NLRP3 signaling activation in THP-1 cells.

2022-08-18 | GSE211210 | GEO

FTO regulates adult neurogenesis through modulating the dynamics of N6-methyladenosine

Project description:Fat mass and obesity-associated gene (FTO) is a member of the Fe (II) and oxoglutarate-dependent AlkB oxygenase family, and has been linked to obesity and intellectual disability. However, the role of FTO in neurodevelopment and neurogenesis remains largely unknown. Here, we show that FTO is expressed in adult neural stem cells (aNSCs) and neurons, and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to the decreased brain size and body weight. We found that FTO deficiency could reduce the proliferation and neuronal differentiation of aNSCs in vivo, which leads to the impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we further performed the genome-wide m6A profiling and observed the dynamic m6A modification during postnatal neurodevelopment. The loss of FTO could lead to the altered m6A modifications on the mRNAs of several key components of BDNF pathway. These results together suggest that FTO play important roles in neurogenesis and learning and memory.

2017-04-20 | GSE94098 | GEO

ALKBH3 Knockdown in PC3 prostate cancer cells

Project description:Background: The oxidative DNA demethylase ALKBH3 targets single-stranded DNA (ssDNA) in order to perform DNA alkylation damage repair. ALKBH3 becomes up-regulated during tumorigenesis and is necessary for proliferation. However, the underlying molecular mechanism remains to be understood. Methods: To further elucidate the function of ALKBH3 in cancer, we performed ChIP-seq to investigate the genomic binding pattern of endogenous ALKBH3 in PC3 prostate cancer cells coupled with microarray experiments to examine the expression effects of ALKBH3 depletion. Results: We demonstrate that ALKBH3 binds to transcription associated locations, such as places of promoter-proximal paused RNA polymerase II and enhancers. Strikingly, ALKBH3 strongly binds to the transcription initiation sites of a small number of highly active gene promoters. These promoters are characterized by high levels of transcriptional regulators, including transcription factors, the Mediator complex, cohesin, histone modifiers and active histone marks. Gene expression analysis showed that ALKBH3 does not directly influence the transcription of its target genes, but its depletion induces an up-regulation of ALKBH3 non-bound inflammatory genes. Conclusions: The genomic binding pattern of ALKBH3 revealed a putative novel hyperactive promoter type. Further, we propose that ALKBH3 is an intrinsic DNA repair protein that suppresses transcription associated DNA damage at highly expressed genes and thereby plays a role to maintain genomic integrity in ALKBH3-overexpressing cancer cells. These results raise the possibility that ALKBH3 may be a potential target for inhibiting cancer progression. PC3 cells were infected with ALKBH3 shRNA or Control shRNA for 48 hours and selected with puromycine. Cells were collected after 48h or 96h past selection.

2015-06-05 | E-GEOD-57568 | biostudies-arrayexpress

Ascorbic acid reprogrames epigenome and epitranscriptome by recycling Fe (III) into Fe (II) in the catalytic cycle of dioxygenases (RNA-Seq)

Project description:Ascorbic acid has been reported to stimulate DNA iterative oxidase TET enzymes, Jumonji C-domain-containinghistone demethylase and potentially RNA m6A demethylase FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status in vitro, in cell lines and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here we systematically investigated the stimulation of ascorbic towards TET2, ALKBH3, histone demethylases and FTO. We find that ascorbic acid reprograms epitranscrip-tome by erasing the hypermethylated m6A sites. Biochemistry and Electron spin resonance (ESR) assays demonstrate that ascorbic acid enters the active pocket of dioxygenases, reduces Fe (III), either incorporated upon protein synthesis or generated upon rebounding the hydroxyl radical during oxidation, into Fe (II). Finally, we propose a new model for the catalytic cycle of dioxygenases by adding in the essential dynamic cofactor, ascorbic acid. Ascorbic acid refreshes and regenerates inactive dioxygenase through recycling Fe (III) into Fe (II) in a dynamic “hit-and-run” manner.

2024-02-01 | GSE242759 | GEO