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Status |
Public on May 21, 2014 |
Title |
Changes in gene expression in BAZ1B knockout and heterozygous targeted clones |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Williams syndrome transcription factor (WSTF) is a multifaceted protein that is involved in several nuclear processes, including replication, transcription, and the DNA damage response. WSTF participates in a chromatin-remodeling complex with the ISWI ATPase, SNF2H, and is thought to contribute to the maintenance of heterochromatin, including at the human inactive X chromosome (Xi). WSTF is encoded by BAZ1B, and is one of twenty-eight genes that are hemizygously deleted in the genetic disorder Williams-Beuren syndrome (WBS). To explore the function of WSTF, we performed zinc finger nuclease-assisted targeting of the BAZ1B gene and isolated several independent knockout clones in human cells. Our results show that, while heterochromatin at the Xi is unaltered, new inappropriate areas of heterochromatin spontaneously form and resolve throughout the nucleus. In three independent mutants, the expression of a large number of genes were impacted, both up and down, by WSTF loss. In addition, we found that cells lacking WSTF responded appropriately to vitamin D treatment, a process we expected to be disrupted. Given the inappropriate appearance of regions of heterochromatin in BAZ1B knockout cells, it is evident that WSTF performs a critical role in maintaining chromatin and transcriptional states. Clearly, further exploration is necessary to fully understand the role of WSTF in maintenance of the epigenome and how WSTF haploinsufficiency contributes to the wide array of symptoms exhibited in WBS patients.
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Overall design |
Samples include three replicate miroarray hybridizations of the parental cells (hTERT-RPE1), three replicates from three independent knock-out clones (D5, F3 and M1), and one set of replicates for a heterozygous mutant clone (A6).
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Contributor(s) |
Culver-Cochran AE, Chadwick BP |
Citation(s) |
24168170 |
Submission date |
May 26, 2013 |
Last update date |
May 28, 2014 |
Contact name |
Brian P Chadwick |
E-mail(s) |
chadwick@bio.fsu.edu
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Phone |
850-645-9279
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Organization name |
Florida State University
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Department |
Biological Science
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Street address |
319 Stadium Drive, King 3076
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City |
Tallahassee |
State/province |
FL |
ZIP/Postal code |
32306 |
Country |
USA |
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Platforms (1) |
GPL16025 |
NimbleGen Homo sapiens Expression Array [100718_HG18_opt_expr] |
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Samples (15)
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Relations |
BioProject |
PRJNA205401 |
Supplementary file |
Size |
Download |
File type/resource |
GSE47390_RAW.tar |
83.3 Mb |
(http)(custom) |
TAR (of PAIR) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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