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Series GSE96659 Query DataSets for GSE96659
Status Public on Mar 15, 2018
Title Novel transcriptional networks regulated by CLOCK in human neurons
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin-immunoprecipitation sequencing for endogenous CLOCK in adult neocortex and RNA-sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts co-expressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks are driven by hub genes with human-specific patterns of expression. Thus, these data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function.
 
Overall design We carried out RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) in differentiated human neural progenitor cells and ChIP-sequencing (ChIP-seq) in both differentiated human neural progenitor cells and BA10 and BA40 of adult human neocortex. For the Chip-seq, five replicates were used for each of the two Brodmann areas (BA10 and BA40) of adult human frozen brain tissue (i.e. the five replicates of BA10 and BA40 came from the same five individuals). For the RNA-seq, three independent replicates of control and CLOCK knockdown samples were used each time point analyzed. For the ATAC-seq, three independent replicates of control and CLOCK knockdown samples were used.
 
Contributor(s) Fontenot M, Berto S, Werthmann G, Usui N, Gleason K, Tamminga C, Takahashi J, Konopka G
Citation(s) 29196536
Submission date Mar 15, 2017
Last update date May 15, 2019
Contact name Genevieve Konopka
E-mail(s) gena@alum.mit.edu
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)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (209)
GSM2537401 ZT20.CLKkd.1 (hi2500)
GSM2537402 ZT20.CLKkd.1 (ns500)
GSM2537403 ZT20.CLKkd.2 (hi2500)
Relations
BioProject PRJNA379305
SRA SRP101959

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
GSE96659_RAW.tar 4.9 Mb (http)(custom) TAR (of BED)
GSE96659_rna-seq.rpkm.txt.tar.gz 16.2 Mb (ftp)(http) TAR
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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