Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity

被引:70
作者
Aapola, U
Liiv, I
Peterson, P [1 ]
机构
[1] Univ Tampere, Tampere Univ Hosp, Inst Med Technol, FIN-33014 Tampere, Finland
[2] Univ Tampere, Tampere Univ Hosp, Dept Pathol, FIN-33014 Tampere, Finland
基金
芬兰科学院;
关键词
D O I
10.1093/nar/gkf474
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3602 / 3608
页数:7
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