Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel role for the conserved, orphan deaminase APOBEC2 [RNA-seq]

ABSTRACT: The AID (activation induced deaminase)/APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of proteins are zinc-dependent cytidine deaminases active on polynucleotides and involved in RNA editing, DNA demethylation or DNA editing. The enzymatic activity, substrate or physiological target(s) of APOBEC2, a member of the AID/APOBEC, remain elusive. Here, we combined next generation sequencing (NGS) techniques with state-of-the-art molecular biology to comprehensively examine the physiological effects of APOBEC2 on the transcriptome and methylome using C2C12 myoblasts differentiating in culture. We also examined APOBEC2’s genome wide-binding specificity. Using RNA sequencing (RNA-seq) by polyA capture, we detected no evidence that APOBEC2 is an RNA editor. In the same system, enhanced reduced representation bisulfite sequencing (eRRBS) data did not support the proposed role of APOBEC2 as a 5-methyl-C (5mC) deaminase. However, chromatin immunoprecipitation sequencing (ChIP-Seq) did reveal specific locations of genomic occupancy of APOBEC2 with a specific motif preference. Combining biochemical, ChIP-Seq and RNA-Seq gene expression analyses we demonstrate that APOBEC2 acts as a negative regulator of gene expression in muscle cells. Our data support a model of APOBEC2 acting as a chromatin-binding factor that leads to inhibition of transcription of genes involved in cell cycle regulation during C2C12 differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE117730 | GEO | 2021/07/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A novel role for the conserved, orphan deaminase APOBEC2 [methylation]

Project description:The AID (activation induced deaminase)/APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of proteins are zinc-dependent cytidine deaminases active on polynucleotides and involved in RNA editing, DNA demethylation or DNA editing. The enzymatic activity, substrate or physiological target(s) of APOBEC2, a member of the AID/APOBEC, remain elusive. Here, we combined next generation sequencing (NGS) techniques with state-of-the-art molecular biology to comprehensively examine the physiological effects of APOBEC2 on the transcriptome and methylome using C2C12 myoblasts differentiating in culture. We also examined APOBEC2’s genome wide-binding specificity. Using RNA sequencing (RNA-seq) by polyA capture, we detected no evidence that APOBEC2 is an RNA editor. In the same system, enhanced reduced representation bisulfite sequencing (eRRBS) data did not support the proposed role of APOBEC2 as a 5-methyl-C (5mC) deaminase. However, chromatin immunoprecipitation sequencing (ChIP-Seq) did reveal specific locations of genomic occupancy of APOBEC2 with a specific motif preference. Combining biochemical, ChIP-Seq and RNA-Seq gene expression analyses we demonstrate that APOBEC2 acts as a negative regulator of gene expression in muscle cells. Our data support a model of APOBEC2 acting as a chromatin-binding factor that leads to inhibition of transcription of genes involved in cell cycle regulation during C2C12 differentiation.

2021-07-26 | GSE117731 | GEO

A novel role for the conserved, orphan deaminase APOBEC2 [ChIP-seq]

2021-07-26 | GSE117729 | GEO

A novel role for the conserved, orphan deaminase APOBEC2

2021-07-26 | GSE117732 | GEO

APOBEC2 Safeguards Skeletal Muscle Cell Fate through Regulating Transcription of Non-Muscle Genes during Myoblast Differentiation

Project description:The apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) family is comprised of nucleic acid editors with roles ranging from antibody diversification to RNA editing. APOBEC2, a member of this family with an evolutionarily conserved nucleic acid binding cytidine deaminase domain, has neither an established substrate nor function. Using a cellular model of muscle differentiation where APOBEC2 is inducibly expressed, we confirmed that APOBEC2 does not have the attributed molecular functions of the APOBEC family, such as RNA editing, DNA demethylation, and DNA mutation. Instead, we found that during muscle differentiation APOBEC2 occupied a specific motif within promoter regions; its removal from those regions resulted in transcriptional changes. Mechanistically, these changes reflect the direct interaction of APOBEC2 with histone deacetylase (HDAC) transcriptional corepressor complexes. We also found that APOBEC2 could bind DNA directly, in a sequence-specific fashion, suggesting that it functions as a recruiter of HDAC to specific genes whose promoters it occupies. These genes are normally suppressed during muscle cell differentiation and their suppression may contribute to the safeguarding of muscle cell fate. Altogether, our results reveal a novel role for APOBEC2 within the APOBEC family.

2024-03-22 | MSV000094388 | MassIVE

Genome-wide identification and functional analysis of Apobec-1 mediated C-to-U RNA editing in mouse small intestine and liver

Project description:Background: RNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoproteinB (apoB) mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Results: Deep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% Sanger sequenced validated), all within 3’ untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression revealed that a subset of targets identified in wild-type mice were restored in Apobec-1 deficient mouse intestine and liver following Apobec-1 rescue. We found distinctive polysome profiles for several RNA editing targets and demonstrated novel exonic editing sites in nuclear preparations from intestine (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice, demonstrating that Apobec-1 is required. Conclusions: These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.

2014-06-02 | PXD001007 | Pride

circRNA sequence authenticity in live cells

Project description:Exogenous RNA, such as circRNA, could be edited by endogenous editors, such as C-to-U editor activation-induced deaminase and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (AID/APOBEC), and A-to-I editor Adenosine deaminases acting on RNA (ADAR) (I: inosine, recognized as G). Editing of circRNA may interfere with IRES and Kozak sequence to initiate antigen translation, and may alter antigen products or mutate stop codons.

2023-12-31 | GSE221086 | GEO

A novel role for the conserved, orphan deaminase APOBEC2 [RNA-seq]

Project description:A novel role for the conserved, orphan deaminase APOBEC2 [RNA-seq]

| PRJNA483032 | ENA

Genome-wide identification and functional analysis of Apobec-1 mediated C-to-U RNA editing in mouse small intestine and liver

Project description:The genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Deep sequencing, data filtering and validation from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% true-positive), all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. We found distinctive polysome profiles for several editing targets and demonstrated nuclear but not cytoplasmic editing of novel exonic sites in intestinal (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice. These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific. Examination of C-to-U RNA editing in mouse liver and intestine

2014-05-23 | E-GEOD-57910 | biostudies-arrayexpress

A novel role for the conserved, orphan deaminase APOBEC2 [ChIP-seq]

Project description:A novel role for the conserved, orphan deaminase APOBEC2 [ChIP-seq]

| PRJNA483033 | ENA

A novel role for the conserved, orphan deaminase APOBEC2

Project description:A novel role for the conserved, orphan deaminase APOBEC2

| PRJNA483031 | ENA