title: A mammalian conserved element derived from SINE displays enhancer properties recapitulating Satb2 expression in early-born callosal projection neurons.
abstract: Short interspersed repetitive elements (SINEs) are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered "junk DNA". However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2(+) neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2(+) neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1(-)/NPY(+)) portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum, a eutherian-specific brain structure.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tashiro
authors.forename: Anne
authors.initials: A
authors.lastname: Teissier
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakanishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kuo
authors.initials: K
authors.lastname: Yan
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.forename: Lisa
authors.initials: L
authors.lastname: Vigier
authors.forename: Kenta
authors.initials: K
authors.lastname: Sumiyama
authors.forename: Mika
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nishihara
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierani
authors.forename: Norihiro
authors.initials: N
authors.lastname: Okada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics*; D003337:Corpus Callosum / Q000166:cytology*; D047108:Embryonic Development / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci / Q000235:genetics; D008322:Mammals / Q000235:genetics*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D026801:Synteny / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; C501473:SATB2 protein, mouse; D014157:Transcription Factors; D001616:beta-Galactosidase