Xenopus MBD3 plays a crucial role in an early stage of development.
DNA methylation plays a crucial role in gene silencing via recruitment of the proteins that specifically recognize methyl-CpG. In the present study, we have shown that two splicing isoforms of MBD3, xMBD3 and xMBD3LF, are the major methyl-CpG binding proteins in Xenopus eggs and early stage embryos. They were highly expressed in the eyes and central nerve system of tadpoles. Inhibition of the expression of xMBD3 by antisense oligonucleotides severely affected embryogenesis. Low-dose injection of antisense oligonucleotides specifically affected eye formation. An identical phenotype was observed on the forced expression of xMBD3 mutated in the methyl-CpG binding domain (MBD) and xMBD3LF, those of which lack methylated DNA binding activity. On the other hand, the eye-defective phenotype was not induced on the injection of truncated forms of mutant xMBD3 or xMBD3LF that contained MBD. We propose that MBD3, distinct from the case in mouse, plays a crucial role in the recognition of methylated genes as an intrinsic component of the complex to guide the corepressor complex during an early stage of Xenopus embryogenesis.
Iwano
Hidetomo
H
Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
Nakamura
Masahiko
M
Tajima
Shoji
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D005123:Eye / Q000196:embryology; D005124:Eye Abnormalities / Q000235:genetics; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2; D008969:Molecular Sequence Data; D010063:Ovum / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D014981:Xenopus; D029867:Xenopus Proteins
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C115368:MBD2 protein; C497395:MECP2 protein, Xenopus; C492013:Mbd3 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins