title: Identification of a transient Sox5 expressing progenitor population in the neonatal ventral forebrain by a novel cis-regulatory element.
abstract: Precise control of lineage-specific gene expression in the neural stem/progenitor cells is crucial for generation of the diversity of neuronal and glial cell types in the central nervous system (CNS). The mechanism underlying such gene regulation, however, is not fully elucidated. Here, we report that a 377 bp evolutionarily conserved DNA fragment (CR5), located approximately 32 kbp upstream of Olig2 transcription start site, acts as a cis-regulator for gene expression in the development of the neonatal forebrain. CR5 is active in a time-specific and brain region-restricted manner. CR5 activity is not detected in the embryonic stage, but it is exclusively in a subset of Sox5+ cells in the neonatal ventral forebrain. Furthermore, we show that Sox5 binding motif in CR5 is important for this cell-specific gene regulatory activity; mutation of Sox5 binding motif in CR5 alters reporter gene expression with different cellular composition. Together, our study provides new insights into the regulation of cell-specific gene expression during CNS development.
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States.
authors: Hailing
authors: H
authors: Hao
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States.
authors: Ying
authors: Y
authors: Li
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States.
authors: Evangeline
authors: E
authors: Tzatzalos
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States.
authors: Jordana
authors: J
authors: Gilbert
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States.
authors: Dhara
authors: D
authors: Zala
authors: The Child Health Institute of New Jersey, 89 French Street, New Brunswick, NJ 08901, United States.
authors: Mantu
authors: M
authors: Bhaumik
authors: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, United States. Electronic address: lcai@rutgers.edu.
authors: Li
authors: L
authors: Cai
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001665:Binding Sites; D002417:Cattle; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D000076104:Oligodendrocyte Transcription Factor 2; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism; D011485:Protein Binding; D055755:SOXD Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D055755:SOXD Transcription Factors; C512773:Olig2 protein, mouse; C089186:Sox5 protein, mouse
keywords: Cis-element; Gene regulation; Neural stem/progenitor cells; Olig2; Sox5; Trans-acting factor