Control of DNMT1 abundance in epigenetic inheritance by acetylation, ubiquitylation, and the histone code.
Inheritance of DNA methylation patterns is a key mechanism involved in epigenetic cell memory transmission from mother cell to daughter cell. This occurs due to cooperation between the DNA methyltransferase DNMT1 and the ubiquitin ligase UHRF1 (ubiquitin-like, containing plant homeo domain and RING finger 1) in a macromolecular complex. Newly identified members of this complex are the acetyltransferase Tip60 (Tat-interactive protein) and the deubiquitinase HAUSP (herpes virus-associated ubiquitin specific protease), which exert tight regulation of DNMT1 abundance through a ubiquitylation-dependent process. It is important to determine how all of these actors communicate with each other and what signals coordinate their communication. In the case of DNMT1, the balance of UHRF1 and HAUSP activities might be influenced by the local environment, such as histone code, cell-cycle status, and local DNA methylation status.
CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, 74 route du Rhin, B.P. 60024, 67401 Illkirch Cedex, France. christian.bronner@unistra.fr
Christian
C
Bronner
D000107:Acetylation; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D042421:Histone Code / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008954:Models, Biological; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination
D022762:CCAAT-Enhancer-Binding Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7