title: Identification of a conserved cis-regulatory element controlling mid-diencephalic expression of mouse Six3.
abstract: The sine oculis homeobox protein Six3 plays pivotal roles in the development of the brain and craniofacial structures. In humans, SIX3 haploinsufficiency results in holoprosencephaly, a defect in anterior midline formation. Although much is known about the evolutionarily conserved functions of Six3, the regulatory mechanism responsible for the expression pattern of Six3 remains relatively unexplored. To understand how the transcription of Six3 is controlled during embryogenesis, we screened ∼300 kb of genomic DNA encompassing the Six3 locus for cis-acting regulatory elements capable of directing reporter gene expression to sites of Six3 transcription in transgenic mouse embryos. We identified a novel enhancer element, whose activity recapitulates endogenous Six3 expression in the ventral midbrain, pretectum, and thalamus. Cross-species comparisons revealed that this Six3 brain enhancer is functionally conserved in other vertebrates. We also showed that normal Six3 transcription in the ventral midbrain and pretectum is dependent on Ascl1, a basic helix-loop-helix proneural factor. Moreover, loss of Ascl1 resulted in downregulation of the Six3 brain enhancer activity, emphasizing its unique role in regulating Six3 expression in the developing brain.
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.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: Jiyeon
authors.initials: J
authors.lastname: Yoon
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: Duc
authors.initials: D
authors.lastname: Tri Lam
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: Jaeseung
authors.initials: J
authors.lastname: Yoon
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: Kwanghee
authors.initials: K
authors.lastname: Baek
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: Yongsu
authors.identifier: 0000-0002-0008-9928
authors.initials: Y
authors.lastname: Jeong
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000097607:Homeobox Protein SIX3
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000097607:Homeobox Protein SIX3; C499317:Ascl1 protein, mouse
keywords: Ascl1; Six3; brain; enhancer