Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene transcription

被引：31

作者：

Ciccarone, Fabio ^{[1
,2
]}

Valentini, Elisabetta ^{[1
,2
]}

Bacalini, Maria Giulia ^{[3
]}

Zampieri, Michele ^{[1
,2
]}

Calabrese, Roberta ^{[1
,2
]}

Guastafierro, Tiziana ^{[1
,2
]}

Mariano, Germano ^{[1
,2
]}

Reale, Anna ^{[1
,2
]}

Franceschi, Claudio ^{[3
]}

Caiafa, Paola ^{[1
,2
]}

机构：

[1] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00185 Rome, Italy

[2] Fdn Cenci Bolognetti, Inst Pasteur, Rome, Italy

[3] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy

来源：

ONCOTARGET | 2014年 / 5卷 / 21期

关键词：

poly(ADP-ribosyl)ation; TET1; DNA methylation; 5-hydroxymethylcytosine; DNA DEMETHYLATION; CHROMATIN-STRUCTURE; TUMOR-SUPPRESSOR; LYSINE RESIDUES; 5-HYDROXYMETHYLCYTOSINE; METHYLATION; PARP-1; 5-METHYLCYTOSINE; PROTEINS; HISTONE;

D O I：

10.18632/oncotarget.1905

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

TET enzymes are the epigenetic factors involved in the formation of the sixth DNA base 5-hydroxymethylcytosine, whose deregulation has been associated with tumorigenesis. In particular, TET1 acts as tumor suppressor preventing cell proliferation and tumor metastasis and it has frequently been found down-regulated in cancer. Thus, considering the importance of a tight control of TET1 expression, the epigenetic mechanisms involved in the transcriptional regulation of TET1 gene are here investigated. The involvement of poly(ADP-ribosyl)ation in the control of DNA and histone methylation on TET1 gene was examined. PARP activity is able to positively regulate TET1 expression maintaining a permissive chromatin state characterized by DNA hypomethylation of TET1 CpG island as well as high levels of H3K4 trimethylation. These epigenetic modifications were affected by PAR depletion causing TET1 downregulation and in turn reduced recruitment of TET1 protein on HOXA9 target gene. In conclusion, this work shows that PARP activity is a transcriptional regulator of TET1 gene through the control of epigenetic events and it suggests that deregulation of these mechanisms could account for TET1 repression in cancer.

引用

页码：10356 / 10367

页数：12

共 62 条

[1] Poly(ADP-ribose)-Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1 [J].