Genome-wide maps of Rai1 binding sites in mouse cortex
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81204 | GEO | 2017/01/03
SECONDARY ACCESSION(S): PRJNA320884
REPOSITORIES: GEO
Similar Datasets
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337750 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337485 | GEO
Project description:The goals of this study are to harvest adult-onset Rai1-deficient mouse brains from hypothalamus and compare the transcriptome with their wild-type littermates. Methods: mRNA profiles from Rai1 conditional knockouts and wild-type mice were generated by deep sequencing, in duplicate using Illumina system. Conclusions: Our study suggests that Rai1 preferentially regulate genes involved in cell communication
2022-01-05 | GSE149952 | GEO
Project description:The goals of this study are to harvest Rai1-deficient mouse brains from multiple tissues and timepoints and compare the transcriptome with their wild-type littermates. Methods: mRNA profiles from Rai1 conditional knockouts and wild-type mice were generated by deep sequencing, in duplicate using Illumina system. Conclusions: Our study suggests that Rai1 preferentially regulate genes involved in cell adhesion and neural projection.
2017-01-03 | GSE81206 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337359 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE336167 | GEO
Project description:To identify Sp7’s molecular interactions in vivo, we used gene-targeting strategies to generate an Sp7-Biotin-3xFLAG knock-in mouse (Sp7-BioFL mouse). This approach appends a biotin (Bio) recognition motif and three copies of the FLAG (FL) epitope at the C-terminus of the Sp7 protein. To validate this knockin system, we compared ChIP-seq results in the MC3T3E1 osteoblast cell line, introducing Sp7 forms that were epitope-tagged at either the N- (N-terminal FLAG tag; MC3_FLAG-Sp7) or C-terminus (C-terminal Biotin-FLAG tag, as in the in vivo targeted allele; MC3_Sp7-BioFLAG). These data show an extensive overlap, suggesting that FLAG tagging at different positions gives comparable outcomes. Second, we examined ChIP on wild-type calvarial primary osteoblasts (POB) using an anti-Sp7 antibody (POB_Sp7Ab-ChIP). The majority of Sp7-Ab ChIP-seq peaks (95%) overlapped with the larger set identified by Sp7-BioFL ChIP-seq.
2016-04-28 | GSE80231 | GEO
Project description:We performed the nascent RNA-seq technique, Bru-Seq, and chromatin immunoprecipitation sequencing (ChIP-seq) for Retinoic acid induced 1 (RAI1) using a custom antibody, on mouse neuronal cultures treated with control or Rai1-targeted shRNA, with 4 hour treatment of vehicle, tetrodoxin (TTX) or bicuculline (BIC) and 20 minute labeling of bromouridine.
2020-06-20 | GSE121749 | GEO
Project description:Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances and stereotypic behaviors. We investigated a cohort of 15 individuals with a clinical suspicion of SMS, who showed neither deletion in the SMS critical region nor damaging variants in RAI1. Potentially deleterious variants were identified in nine of these subjects using whole-exome sequencing. Eight of these changes affect KMT2D, ZEB2, MAP2K2, GLDC, CASK, MECP2, KDM5C and POGZ, known to be associated with Kabuki syndrome 1, Mowat-Wilson syndrome, cardiofaciocutaneous syndrome, glycine encephalopathy, mental retardation and microcephaly with pontine and cerebellar hypoplasia, X-linked mental retardation 13, X-linked mental retardation Claes-Jensen type and White-Sutton syndrome, respectively. The ninth individual carries a de novo variant in JAKMIP1, a regulator of neuronal translation that was recently found deleted in a patient with autism spectrum disorder. Analyses of coexpression and biomedical text mining suggest that these pathologies and SMS are part of the same disease network. Further support for this hypothesis was obtained from transcriptome profiling that showed that the expression levels of both Zeb2 and Map2k2 are perturbed in Rai1-/- mice. As an orthogonal approach to potentially contributory disease gene variants, we used chromatin conformation capture to reveal chromatin contacts between RAI1 and the loci flanking ZEB2 and GLDC, as well as between RAI1 and human orthologs of the genes that show perturbed expression in our Rai1-/- mouse model. These holistic studies of RAI1 and its interactions allow insights into SMS and other disorders associated with intellectual disability and behavioral abnormalities. Our findings support a pan-genomic approach to the molecular diagnosis of a distinctive disorder.
2017-02-12 | GSE83420 | GEO
Project description:Mouse 129-B13 ESCs were genetically modified using CRISPR-Cas9 with two guides to remove exon 4 of Rai1, single-cell sorted and expanded to establish modified cell lines. Additionally, cell lines derived from unsuccessfully modified lines were used as "wild-type" controls. 3 lines of each group were used as biological replicates. Samples were differentiated from mouse ESCs (Day 0) to neural progenitor cells (Day 8) and glutamatergic neurons (Day 12). NEBNext Poly(A) mRNA Magnetic Isolation Module was used to enrich mRNA. Nonsense-mediated decay was not observed in Rai1 ex 4 KOs.
2023-01-31 | E-MTAB-10490 | biostudies-arrayexpress