Inhibition of DNA binding of Sox2 by the SUMO conjugation.
Sox2 is a member of the high mobility group (HMG) domain DNA-binding proteins for transcriptional control and chromatin architecture. The HMG domain of Sox2 binds the DNA to facilitate transactivation by the cooperative transcription factors such as Oct3/4. We report that mouse Sox2 is modified by SUMO at lysine 247. Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2. By contrast with the unmodified form, Sox2 fused to SUMO-1 did not augment transcription via the Fgf4 enhancer in the presence of Oct3/4. Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer. These indicate that Sox2 sumoylation negatively regulates its transcriptional role through impairing the DNA binding.
Tsuruzoe
Shu
S
Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Ishihara
Ko
K
Uchimura
Yasuhiro
Y
Watanabe
Sugiko
S
Sekita
Yoko
Y
Aoto
Takahiro
T
Saitoh
Hisato
H
Yuasa
Yasuhito
Y
Niwa
Hitoshi
H
Kawasuji
Michio
M
Baba
Hideo
H
Nakao
Mitsuyoshi
M
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D051519:Fibroblast Growth Factor 4 / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D055748:SOXB1 Transcription Factors; D025842:SUMO-1 Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D050814:Octamer Transcription Factor-3; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D025842:SUMO-1 Protein; C527783:Sox2 protein, mouse; D015534:Trans-Activators; D004247:DNA; D008239:Lysine