title: Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain.
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.
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Bumwhee
authors.initials: B
authors.lastname: Lee
authors.forename: Hobeom
authors.initials: H
authors.lastname: Song
authors.forename: Karine
authors.initials: K
authors.lastname: Rizzoti
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Son
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Yoon
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
authors.forename: Yongsu
authors.initials: Y
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D000097607:Homeobox Protein SIX3; C465570:Shh protein, mouse; C527783:Sox2 protein, mouse
keywords: ChIP Display; Forebrain; Mouse; Six3; Sox2