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Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2004 Jan 29; Vol. 32 (2), pp. 598-610. Date of Electronic Publication: 2004 Jan 29 (Print Publication: 2004). - Publication Year :
- 2004
-
Abstract
- The de novo DNA methyltransferase Dnmt3a is one of three mammalian DNA methyltransferases that has been shown to play crucial roles in embryonic development, genomic imprinting and transcriptional silencing. Despite its importance, very little is known about how the enzymatic activity and transcriptional repression functions of Dnmt3a are regulated. Here we show that Dnmt3a interacts with multiple components of the sumoylation machinery, namely the E2 sumo conjugating enzyme Ubc9 and the E3 sumo ligases PIAS1 and PIASxalpha, all of which are involved in conjugating the small ubiquitin-like modifier polypeptide, SUMO-1, to its target proteins. Dnmt3a is modified by SUMO-1 in vivo and in vitro and the region of Dnmt3a responsible for interaction maps to the N-terminal regulatory domain. Functionally, sumoylation of Dnmt3a disrupts its ability to interact with histone deacetylases (HDAC1/2), but not with another interaction partner, Dnmt3b. Conditions that enhance the sumoylation of Dnmt3a in vivo abolish its capacity to repress transcription. These studies reveal a new level of regulation governing Dnmt3a whereby a post-translational modification can dramatically regulate its interaction with specific protein partners and alter its ability to repress transcription.
- Subjects :
- Animals
Binding Sites
Cell Line
DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors
DNA (Cytosine-5-)-Methyltransferases chemistry
DNA Methyltransferase 3A
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Humans
Kruppel-Like Transcription Factors
Mice
Protein Binding
Protein Inhibitors of Activated STAT
Protein Structure, Tertiary
Proteins metabolism
Repressor Proteins antagonists & inhibitors
Repressor Proteins chemistry
SUMO-1 Protein chemistry
Transcription Factors genetics
Transcription Factors metabolism
Ubiquitin-Conjugating Enzymes metabolism
Ubiquitin-Protein Ligases metabolism
DNA (Cytosine-5-)-Methyltransferases metabolism
Gene Silencing
Histone Deacetylases metabolism
Protein Processing, Post-Translational
Repressor Proteins metabolism
SUMO-1 Protein metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 14752048
- Full Text :
- https://doi.org/10.1093/nar/gkh195