Abstract
Methylation of cytosines at CpG dinucleotides is essential for mammalian development. MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of proteins that contain a methyl-CpG binding domain (MBD). Except for MBD4, these proteins are involved in gene silencing imposed by methylated DNA. We have identified a human gene that codes for a protein that is 42% identical to MBD3 and 38% identical to MBD2 but lacks the methyl-CpG binding domain. The recombinant protein does not bind to methylated DNA in vitro. The corresponding mouse Mbd3L1 gene was also cloned. The MBD3L1 gene is expressed specifically in testis. During spermatogenesis, expression of MBD3L1 is observed only in round spermatids, suggesting a role for the gene product in the postmeiotic stages of male germ cell development. The MBD3L1 protein is localized to discrete areas in the nucleus and contains an N-terminal transcriptional repression domain. This repression is independent of histone deacetylase inhibition. A homologue of MBD3L1, MBD3L2, was also identified and cloned. Expression of MBD3L2 was found in germ cell tumors and some somatic tissues. These novel proteins may function as counterparts of MBD2 and/or MBD3 in developmental stage-specific transcriptional repression.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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COS Cells
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Cell Nucleus / metabolism
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Cloning, Molecular
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DNA / genetics
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DNA / metabolism
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DNA Methylation
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics*
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Female
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Gene Expression
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Green Fluorescent Proteins
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Humans
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Luciferases / genetics
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Luciferases / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Male
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Mice
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Molecular Sequence Data
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Promoter Regions, Genetic / genetics
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Protein Binding
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RNA / genetics
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RNA / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Testis / metabolism*
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Transcription Factors
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Transcription, Genetic
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Transfection
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Luminescent Proteins
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MBD2 protein
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MBD3 protein, human
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MBD3L1 protein, human
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MBD3L2 protein, human
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Mbd3 protein, mouse
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Recombinant Fusion Proteins
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Repressor Proteins
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Transcription Factors
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Green Fluorescent Proteins
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RNA
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DNA
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Luciferases
Associated data
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GENBANK/AF503919
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GENBANK/AF503920
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GENBANK/AY038022
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GENBANK/AY038023