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Dev Biol. 2013 Sep 15;381(2):491-501. doi: 10.1016/j.ydbio.2013.06.016. Epub 2013 Jun 19.

Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain.

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1
Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.

Abstract

The SRY-related HMG box transcription factor Sox2 plays critical roles throughout embryogenesis. Haploinsufficiency for SOX2 results in human developmental defects including anophthalmia, microphthalmia and septo-optic dysplasia, a congenital forebrain defect. To understand how Sox2 plays a role in neurogenesis, we combined genomic and in vivo transgenic approaches to characterize genomic regions occupied by Sox2 in the developing forebrain. Six3, a homeobox gene associated with holoprosencephaly, a forebrain midline defect, was identified as a Sox2 transcriptional target. This study shows that Sox2 directly regulates a previously unidentified long-range forebrain enhancer to activate Six3 expression in the rostral diencephalon. Further biochemical and genetic evidences indicated a direct regulatory link between Sox2 and Six3 during forebrain development, providing a better understanding of a common molecular mechanism underlying these forebrain defects.

KEYWORDS:

ChIP Display; Forebrain; Mouse; Six3; Sox2

PMID:
23792023
DOI:
10.1016/j.ydbio.2013.06.016
[Indexed for MEDLINE]
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