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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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.
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| Contributor(s) |
Sun J, Rockowitz S, Xie Q, Ashery-Padan R, Zheng D, Cvekl A |
| Citation(s) |
26138486, 26330747, 38643244 |
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| Submission date |
Mar 16, 2015 |
| Last update date |
May 17, 2024 |
| Contact name |
Shira Rockowitz |
| Organization name |
Albert Einstein College of Medicine
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| Street address |
1300 Morris Park Ave
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| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10461 |
| Country |
USA |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA278473 |
| SRA |
SRP056219 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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