ADNP suppresses R-loops at its binding sites
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA719393 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14136052_1.fastq.gz | Fastqsanger.gz | |||
| SRR14136052_2.fastq.gz | Fastqsanger.gz | |||
| SRR14136059_1.fastq.gz | Fastqsanger.gz | |||
| SRR14136059_2.fastq.gz | Fastqsanger.gz | |||
| SRR14136060_1.fastq.gz | Fastqsanger.gz |
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Project description:We have identified ADNP as an R-loop regulator using a proximity-dependent labeling system. We find that ADNP is necessary to suppress R-loops at its binding sites, and that deletion of the ADNP homeodomain reduces ADNP binding to chromatin and results in R-loop accumulation.
2021-11-15 | GSE171401 | GEO
Project description:Activity-dependent neuroprotective protein (ADNP) is one of the most frequent autism spectrum disorder-associated gene products known to date. Here we show that Adnp interacts with the chromatin remodeler Chd4 and the heterochromatin protein HP1 to form a stable complex, which we refer to as ChAHP. Genetic ablation of ChAHP components or DNA binding sites in embryonic stem cells prematurely activates lineage-specific genes, revealing an important role for Adnp in restraining the differentiation capacity of pluripotent cells. Adnp targets the ChAHP complex to specific sequence motifs at euchromatic loci, representing an H3K9 methylation-independent mechanism of HP1 recruitment and gene silencing.
2018-05-23 | GSE97945 | GEO
Project description:The putative transcription factor, activity-dependent neuroprotective protein (ADNP) is a zinc finger and homeodomain - like profile containing protein. ADNP knockout mice die at day 9 of gestation. To reveal ADNP-associated pathways, a 22,690- Affymetrix probe array was used on ADNP knockout and control embryos. References:; Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem. 1999 Mar;72(3):1283-93. PMID: 10037502 [PubMed - indexed for MEDLINE]; Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem. 2001 Jan 5;276(1):708-14. PMID: 11013255 [PubMed - indexed for MEDLINE]; Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res Dev Brain Res. 2003 Aug 12;144(1):83-90. PMID: 12888219 [PubMed - indexed for MEDLINE] Experiment Overall Design: To identify downstream target genes of ADNP, we examined global gene expression profiles of whole E9 knockout embryos (KO - ADNP -l-), their wild-type (WT - ADNP +l+ ) and their heterozygous (H - ADNP âl+ ) littermates, using the Affymetrix Murine Genome 430A oligonucleotide microarrays. Gestation day 9 was chosen as it is the period at which embryos lacking ADNP exhibit distinct morphological and developmental changes prior to degeneration and in uterus absorption. Total RNA was extracted from four ADNP knockout embryos, four normal embryos and six heterozygous embryos. A pool of two genotype identical littermates was used on seven different arrays (pooling of two embryos was necessary to obtain enough RNA on each of the gene microarrays).
2008-06-12 | E-GEOD-4068 | biostudies-arrayexpress
Project description:In order to investigate the functions of the zinc finger transcription regulator ZMYM2 and the different types of ZMYM2 binding complex with TRIM28 or ADNP, we generated the ChIP-seq data of ADNP or TRIM28 in U2OS cells.
2023-06-01 | E-MTAB-12292 | biostudies-arrayexpress
Project description:R-loops are three stranded nucleic acid structures that accumulate on chromatin in neurological diseases and cancers and that contribute to genome instability. Using a proximity-dependent labeling system, we identified distinct classes of proteins that regulate R-loops in vivo through different mechanisms. We show that ATRX suppresses R-loops by interacting with RNAs and preventing R-loop formation. Our proteomics screen also discovered an unexpected enrichment for proteins containing zinc fingers and homeodomains at R-loops. One of the most consistently enriched proteins at R-loops was activity-dependent neuroprotective protein (ADNP), which is frequently mutated in ASD and causal in ADNP syndrome. We find that ADNP is necessary to suppress R-loops in vivo at its genomic targets and that it resolves R-loops in vitro. Furthermore, deletion of the homeodomain severely diminishes R-loop resolution activity in vitro, results in R-loop accumulation at ADNP targets and compromises neuronal differentiation. Notably, patient derived human induced pluripotent stem cells that contain an ADNP syndrome-causing mutation exhibit R-loop and CTCF accumulation at ADNP targets. Our findings point to a specific role for ADNP-mediated R-loop resolution in physiological and pathological neuronal function and, more broadly, to a previously unappreciated role for zinc finger and homeodomain proteins in R-loop regulation, with important implications for developmental disorders and cancers.
2021-06-03 | MSV000087568 | MassIVE
Project description:We have defined the tumor and tumor suppressor signature for Meis1 and Prep1 (pKnox1), respectively, using ChIP-seq and RNA-seq in a cell system in which tumor suppressor Prep1 and oncogene Meis1 compete for tumorigenesis [GSE54221; GSE58802]. In this paper we report that the number of Meis1 or Prep1 DNA binding sites increases linearly with the level of expression of the two transcription factors. Overexpression of Meis1 induces tumors. At the molecular level it modifies the DNA target specificity by increasing the number of low-affinity binding sites, which results in a different choice of consensus sequences with predominance of sites normally bound by the AP1 transcription factor family. Upon concomitant overexpression of Prep1 and Meis1 tumorigenesis is inhibited. Prep1 dominates over Meis1 not only because it partially decreases Meis1 protein level but also because it prevents the binding to a substantial fraction of the low affinity binding sites. Overall, overexpression of Prep1 reverses the nature of the bound and regulated genes from stimulatory to inhibitory of signal transduction and transcription, which suppresses tumorigenesis. By identifying the Meis1 tumor signature, specific relevant signaling pathways are identified. In line with these results, tumorigenic Meis1-overexpressing cells are uniquely hypersensitive to inhibitors of the MAPK/Akt pathways. Examination of Prep1 and Meis1 in five cell type
2016-06-25 | E-GEOD-58818 | biostudies-arrayexpress
Project description:We report age-differential synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIa hyperactivity in Adnp-mutant mice. These mice show impaired and inflexible contextual learning and memory along with social and anxiety-related deficits in adults, long after the juvenile-stage decrease of ADNP protein levels to ~10% of the newborn level. Adnp-mutant mice show abnormally enhanced long-term potentiation in adults but not in juveniles. This is accompanied by CaMKIIa hyperactivity involving increased baseline autophosphorylation and altered phosphorylation of CaMKIIa substrates, as revealed by unbiased proteomic analyses.
2023-07-11 | PXD037325 | Pride
Project description:In order to investigate the functions of the zinc finger transcription regulator ZMYM2 and the different types of ZMYM2 binding complex with TRIM28 or ADNP, we generated the RNA-seq data with ZMYM2, TRIM28 or ADNP siRNA in U2OS cells and the control cases with siNT in U2OS cells as well.
2023-06-01 | E-MTAB-12291 | biostudies-arrayexpress
Project description:ADNP syndrome, involving the ADNP transcription factor in the SWI/SNF chromatin-remodeling complex, is characterized by developmental delay, intellectual disability, and autism spectrum disorders (ASD). In ASD, ADNP is a highly penetrant risk gene, accounting for ~0.17% cases. Although Adnp-haploinsufficient mice display various phenotypic deficits, the underlying synaptic mechanisms are poorly understood. Here we report age-differential synaptic plasticity deficits associated with cognitive inflexibility and CaMKIIα hyperactivity in Adnp-mutant mice. These mice show impaired and inflexible contextual learning and memory additional to social and anxiety-related deficits in adults long after a marked decrease in ADNP protein levels to ~10% of newborn levels in juveniles. In addition, Adnp-mutant adults show abnormally enhanced long-term potentiation in adults but not in juveniles. This accompanies CaMKIIα hyperactivity involving increased baseline autophosphorylation, as revealed by unbiased proteomic analyses. Therefore, ADNP haploinsufficiency in mice leads to cognitive inflexibility involving altered synaptic plasticity and signaling in adults long after a marked decrease in Adnp expression in juveniles.
2023-07-11 | GSE213354 | GEO
Project description:Ybx1 binding sites and Ybx1-binding m5C sites in zebrafish embryo sample.
| PRJNA493828 | ENA