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GEO help: Mouse over screen elements for information. |
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Status |
Public on Aug 28, 2020 |
Title |
Characterization of SALL2 gene isoforms and its targets across cell types reveals highly conserved networks |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The SALL2 transcription factor (TF), an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation and considered as a tumor suppressor in certain human cancers. Several transcriptional targets of SALL2 are identified, these include the p21CDKN1A and p16INK4A cyclin-dependent kinase inhibitors, and the PMAIP1 and Bax pro-apoptotic genes, among others in various cell types. The human and mouse SALL2 gene loci contain two promoters, each one controlling the expression of a different protein isoform (namely E1 and E1A). However, several improvements on the human genome assembly and gene annotation through next-generation sequencing technologies over time reveal correction and annotation of additional isoforms, obscuring dissection of SALL2 isoform-specific transcriptional targets. We here integrated current data of normal/tumor gene expression databases along with ChIP-seq binding profiles to analyze SALL2 isoforms expression distribution and infer isoform-specific SALL2 targets. We found that the canonical SALL2 isoform (E1) is one of the lowest expressed, while isoform E1A is highly predominant across cell types. To dissect SALL2 isoform-specific targets, we analyzed publicly available ChIP-seq data from glioblastoma multiforme (GBM) and in-house ChIP-seq datasets performed in SALL2 wild-type and isoform E1A knockout HEK293 cells. Another available ChIP-seq data in HEK293 cells (ENCODE Consortium Phase III) overexpressing a non-canonical SALL2 isoform (herein named short_E1A) was analyzed but not included in the final analysis because we demonstrated that short_E1A is mostly localized in the cytoplasm, making impractical to dissect its direct transcriptional targets in this cell model. Regardless of cell type, our analysis reveals a highly conserved network of brain-specific TFs (i.e., SALL3, POU3F2, and NPAS3) and PODXL as a gene that is likely regulated by SALL2 across cell types. Our data integration identified a conserved molecular network in which SALL2 regulates target genes and encourages validation of publicly available ChIP-seq datasets for assessing transcriptional targets of a specific gene/isoform.
Financial support: This work was supported by Fondecyt Regular Grants #1151031, #1191172 to Roxana Pincheira Fondecyt Regular Grant #120 to Ariel Castro, Postdoctorate Fondecyt Grant #3160129 and Fondecyt de Iniciacion # 1119028 to Matias I.Hepp.
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Overall design |
ChIP-seq of endogenous SALL2 performed in wild-type HEK293 cells, SALL2 E1A knockout isoforms in HEK293 cells and SALL2 total knockout in HEK293 cells
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Contributor(s) |
Farkas C, Hepp M, Pincheira R |
Citation(s) |
33692826 |
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Submission date |
Feb 26, 2020 |
Last update date |
Mar 13, 2021 |
Contact name |
Carlos Farkas |
E-mail(s) |
cfarkas@udec.cl
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Phone |
994052209
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Organization name |
Universidad de Concepción (UDEC)
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Department |
Bioquímica y Biología Molecular
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Lab |
TSC lab
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Street address |
Chacabuco 1140, 1808
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City |
Concepción |
State/province |
Biobío |
ZIP/Postal code |
4030000 |
Country |
Chile |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (3) |
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Relations |
BioProject |
PRJNA608852 |
SRA |
SRP250784 |
Supplementary file |
Size |
Download |
File type/resource |
GSE145940_RAW.tar |
195.1 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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