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Series GSE55840 Query DataSets for GSE55840
Status Public on Jun 13, 2014
Title Transcription Factor Network Specifying Inhibitory versus Excitatory Neurons in the Dorsal Spinal Cord [ChIP-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system.   In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification.
Overall design Examination of Ascl1 and Ptf1a genome-wide binding in developing neural tube.
Contributor(s) Borromeo MD, Meredith DM, Castro DS, Chang JC, Tung K, Guillemot F, Johnson JE
Citation(s) 24924197
Submission date Mar 12, 2014
Last update date May 15, 2019
Contact name Jane E Johnson
Organization name UT Southwestern Medical Center
Department Neuroscience
Street address 5323 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390-9111
Country USA
Platforms (2)
GPL9185 Illumina Genome Analyzer (Mus musculus)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (6)
GSM1347006 Ascl1_ChIP
GSM1347007 Ascl1_Input_Ctrl
GSM1347008 ChIP-seq_Ptf1a_NT_2
This SubSeries is part of SuperSeries:
GSE55841 Transcription Factor Network Specifying Inhibitory versus Excitatory Neurons in the Dorsal Spinal Cord
BioProject PRJNA241117
SRA SRP040024

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

Supplementary file Size Download File type/resource
GSE55840_RAW.tar 303.8 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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