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Series GSE66961 Query DataSets for GSE66961
Status Public on Jul 09, 2015
Title Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during lens and forebrain development
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using lens and forebrain chromatin from mice. A total of 3,723 (forebrain) and 3,514 (lens) Pax6-containing peaks were identified, with ~70% of them found in both tissues and thereafter called “common” peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, -PD/HD and -HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit control via components of FGF (Fgfr2, Ccnd1, and Prox1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis.
Overall design Examination of Pax6 in mouse embryonic forebrain and newborn lens. We performed ChIP-seq on mouse E12.5 embryonic forebrain and newborn lens. Genome-wide binding sites of Pax6, H3K4me1, H3K4me3, H3K27ac, H3K27me3, and Pol2 were generated. We also performed RNA-seq on mouse E12.5 embryonic forebrain and newborn lens epithelial cells and fibers.
Contributor(s) Sun J, Rockowitz S, Xie Q, Ashery-Padan R, Zheng D, Cvekl A
Citation(s) 26138486, 26330747, 38643244
Submission date Mar 16, 2015
Last update date May 17, 2024
Contact name Shira Rockowitz
Organization name Albert Einstein College of Medicine
Street address 1300 Morris Park Ave
City Bronx
State/province NY
ZIP/Postal code 10461
Country USA
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (24)
GSM1635068 forebrain_Pax6_ChIPseq_rep1
GSM1635069 forebrain_Pax6_ChIPseq_rep2
GSM1635070 forebrain_input_3
BioProject PRJNA278473
SRA SRP056219

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Supplementary file Size Download File type/resource
GSE66961_RAW.tar 6.0 Mb (http)(custom) TAR (of BED, NARROWPEAK, TXT)
GSE66961_fb_Pax6_macs2_peaks.narrowPeak.gz 79.7 Kb (ftp)(http) NARROWPEAK
GSE66961_gene.rpkm.matrix.txt.gz 307.3 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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