Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells.
Sox family transcription factors play essential roles in cell differentiation, development, and sex determination. Sox2 was previously thought to be the sole Sox protein expressed in mouse embryonic stem (ES) cells. Sox2 associates with Oct3/4 to maintain self-renewal of ES cells. In the current study, digital differential display identified transcripts for an additional Sox family member, Sox15, enriched in mouse ES cells. Reverse transcription-PCR confirmed that Sox15 expression is highest in undifferentiated ES cells and repressed upon differentiation. Sox15 is expressed at low levels in several tissues, including testis and muscle. In vitro studies showed that Sox15, like Sox2, associated with Oct3/4 on DNA sequences containing the octamer motif and Sox-binding site. Gel mobility shift assays and SELEX analyses showed that Sox15 binds similar DNA sequences as Sox2 but with weaker affinity. In contrast to the early embryonic lethality observed in Sox2-null mice, Sox15-null ES cells and mice were grossly normal. DNA microarray analyses revealed that Otx2, Ctgf, Ebaf, and Hrc are dysregulated in Sox15-null ES cells, however. Chromatin immunoprecipitation showed that Sox15, but not Sox2, bound to a Sox consensus binding site within the Hrc gene. Taken together, these data demonstrate differential roles for Sox15 and Sox2 in transcriptional control in mouse ES cells.
Maruyama
Masayoshi
M
Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Ichisaka
Tomoko
T
Nakagawa
Masato
M
Yamanaka
Shinya
S
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D015139:Blotting, Southern; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology*; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D005822:Genetic Vectors; D005838:Genotype; D006609:High Mobility Group Proteins / Q000502:physiology*; D047468:Immunoprecipitation; D008024:Ligands; D051379:Mice; D008957:Models, Genetic; D050814:Octamer Transcription Factor-3; D020411:Oligonucleotide Array Sequence Analysis; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055747:SOX Transcription Factors; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000378:metabolism*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D000099254:Organic Cation Transporter 3
D004247:DNA; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D008024:Ligands; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D055747:SOX Transcription Factors; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000099254:Organic Cation Transporter 3; C494174:Pou5f1 protein, mouse; C080886:Sox15 protein, mouse; C527783:Sox2 protein, mouse