Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity
AUTOR(ES)
Aapola, Ulla
FONTE
Oxford University Press
RESUMO
DNMT3L is a regulator of imprint establishment of normally methylated maternal genomic sequences. DNMT3L shows high similarity to the de novo DNA methyltransferases, DNMT3A and DNMT3B, however, the amino acid residues needed for DNA cytosine methyltransferase activity have been lost from the DNMT3L protein sequence. Apart from methyltransferase activity, Dnmt3a and Dnmt3b serve as transcriptional repressors associating with histone deacetylase (HDAC) activity. Here we show that DNMT3L can also repress transcription by binding directly to HDAC1 protein. We have identified the PHD-like zinc finger of the ATRX domain as a main repression motif of DNMT3L, through which DNMT3L recruits the HDAC activity needed for transcriptional silencing. Furthermore, we show that DNMT3L protein contains an active nuclear localisation signal at amino acids 156–159. These results describe DNMT3L as a co-repressor protein and suggest that a transcriptionally repressed chromatin organisation through HDAC activity is needed for establishment of genomic imprints.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=134241Documentos Relacionados
- Dnmt3L is a transcriptional repressor that recruits histone deacetylase
- The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a
- Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo
- Histone deacetylase inhibition is associated with transcriptional repression of the Hmga2 gene
- Smad-Dependent Recruitment of a Histone Deacetylase/Sin3A Complex Modulates the Bone Morphogenetic Protein-Dependent Transcriptional Repressor Activity of Nkx3.2