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- 저자 : Rizzoti, Karine (검색결과 2 건)
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Lee, Bumwhee,Rizzoti, Karine,Kwon, David S.,Kim, Seon-Young,Oh, Sangtaek,Epstein, Douglas J.,Son, Youngsook,Yoon, Jaeseung,Baek, Kwanghee,Jeong, Yongsu Elsevier 2012 Developmental biology Vol.366 No.2
<P><B>Abstract</B></P><P>Six6, a <I>sine oculis</I> homeobox protein, plays a crucial and conserved role in the development of the forebrain and eye. To understand how the expression of <I>Six6</I> is regulated during embryogenesis, we screened ∼250kb of genomic DNA encompassing the <I>Six6</I> locus for <I>cis</I>-regulatory elements capable of directing reporter gene expression to sites of <I>Six6</I> transcription in transgenic mouse embryos. Here, we describe two novel enhancer elements, that are highly conserved in vertebrate species and whose activities recapitulate <I>Six6</I> expression in the ventral forebrain and eye, respectively. Cross-species comparisons of the <I>Six6</I> forebrain enhancer sequences revealed highly conserved binding sites matching the consensus for homeodomain and SoxB1 transcription factors. Deletion of either of the binding sites resulted in loss of the forebrain enhancer activity in the ventral forebrain. Moreover, our studies show that members of the <I>SoxB1</I> family, including <I>Sox2</I> and <I>Sox3</I>, are expressed in the overlapping region of the ventral forebrain with <I>Six6</I> and can bind to the <I>Six6</I> forebrain enhancer. Loss of function of <I>SoxB1</I> genes <I>in vivo</I> further emphasizes their role in regulating <I>Six6</I> forebrain enhancer activity. Thus, our data strongly suggest that SoxB1 transcription factors are direct activators of <I>Six6</I> expression in the ventral forebrain.</P> <P><B>Highlights</B></P><P>► We identify regulatory elements to control <I>Six6</I> expression in the ventral forebrain and eye. ► The forebrain <I>Six6</I> enhancer is dependent on homeodomain and SoxB1 binding sites. ► SoxB1 binds and activates the <I>Six6</I> forebrain enhancer. ► <I>SoxB1</I> mutants fail to activate <I>Six6</I> transcription in the ventral forebrain.</P>
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Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain
Lee, B.,Song, H.,Rizzoti, K.,Son, Y.,Yoon, J.,Baek, K.,Jeong, Y. Academic Press 2013 Developmental biology Vol.381 No.2
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.
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