Sox2 Transcriptionally Regulates Pqbp1, an Intellectual Disability-Microcephaly Causative Gene, in Neural Stem Progenitor Cells

Chan Li, Hikaru Ito, Kyota Fujita, Hiroki Shiwaku, Yunlong Qi, Kazuhiko Tagawa, Takuya Tamura, Hitoshi Okazawa

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

PQBP1 is a nuclear-cytoplasmic shuttling protein that is engaged in RNA metabolism and transcription. In mouse embryonic brain, our previous in situ hybridization study revealed that PQBP1 mRNA was dominantly expressed in the periventricular zone region where neural stem progenitor cells (NSPCs) are located. Because the expression patterns in NSPCs are related to the symptoms of intellectual disability and microcephaly in PQBP1 gene-mutated patients, we investigated the transcriptional regulation of PQBP1 by NSPC-specific transcription factors. We selected 132 genome sequences that matched the consensus sequence for the binding of Sox2 and POU transcription factors upstream and downstream of the mouse PQBP1 gene. We then screened the binding affinity of these sequences to Sox2-Pax6 or Sox2-Brn2 with gel mobility shift assays and found 18 genome sequences that interacted with the NSPC-specific transcription factors. Some of these sequences had cis-regulatory activities in Luciferase assays and in utero electroporation into NSPCs. Furthermore we found decreased levels of expression of PQBP1 protein in NSPCs of heterozygous Sox2-knockout mice in vivo by immunohistochemistry and western blot analysis. Collectively, these results indicated that Sox2 regulated the transcription of PQBP1 in NSPCs.

Original languageEnglish (US)
Article numbere68627
JournalPloS one
Volume8
Issue number7
DOIs
StatePublished - Jul 16 2013

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