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Series GSE230914 Query DataSets for GSE230914
Status Public on May 02, 2023
Title Control of cell identity and early neuronal fate commitment by the enhancer module of Integrator [Hi-C]
Organism Homo sapiens
Experiment type Other
Summary Cell fate specification occurs via coordinated transcriptional changes in pluripotent cells, resulting in progressive commitment towards distinct lineages. Lineage-specific transcription factors (TFs), through their intrinsic DNA-binding ability, operate as master orchestrators of early and late developmental processes by turning on select cis-regulatory enhancers and proximal promoter elements. TF binding ultimately drives recruitment of the basal transcriptional machinery that comprises RNA Polymerase II (RNAPII) and a host of polymerase-associated multiprotein complexes, including the metazoan-specific Integrator complex. Integrator is primarily known to modulate RNAPII processivity and to surveil RNA integrity. Here we show that a set of Integrator subunits (enhancer module) plays a direct role in cell fate specification by promoting epigenetic changes and TF binding at enhancer elements that drive neurogenesis and maintain neuronal cell identity. Depletion of a single Integrator subunit (INTS10) results in loss of molecular and morphological neuronal features, while diverting progenitor cells towards mesenchymal identity. Commissioning of developmental enhancers rely on Integrator’s enhancer module, which stabilizes SOX2 binding at chromatin upon exit from pluripotency. Integrator therefore operates as a functional bridge between enhancers and target promoters and is a driver of early developmental processes, providing new insight into a growing family of neurodevelopmental syndromes.
 
Overall design Hi-C was done in WT and INTS10heterzyogote NPCs.
 
Contributor(s) Hill C, Gardini A
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Submission date Apr 28, 2023
Last update date May 04, 2023
Contact name Alessandro Gardini
E-mail(s) agardini@wistar.org
Phone 2158983755
Organization name The Wistar Institute
Lab Gardini Lab
Street address 3601 Spruce St, Room 230
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (2)
GSM7246729 NPC, WT, HiC, biol rep1
GSM7246730 NPC, INTS10HET2, HiC, biol rep1
This SubSeries is part of SuperSeries:
GSE230928 Control of cell identity and early neuronal fate commitment by the enhancer module of Integrator
Relations
BioProject PRJNA962922

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE230914_RAW.tar 22.4 Mb (http)(custom) TAR (of COOL, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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