RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

Girard N.; Tremblay M.; Humbert M.Grondin B.Haman A.Labrecque J.Chen B.Chen Z.Chen S.-J.Hoang T.

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RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

机译：RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

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In acute promyelocytic leukemia, granulocytic differentiation is arrested at the promyelocyte stage. The variant t(11;17) translocation produces two fusion proteins, promyelocytic leukemia zinc finger-retinoic acid receptor ? (PLZF-RAR?) and RAR?-PLZF, both of which participate in leukemia development. Here we provide evidence that the activity of CCAAT/enhancer binding protein ? (C/EBP?), a master regulator of granulocytic differentiation, is severely impaired in leukemic promyelocytes with the t(11;17) translocation compared with those associated with the t(15;17) translocation. We show that RAR?-PLZF inhibits myeloid cell differentiation through interactions with C/EBP? tethered to DNA, using ChIP and DNA capture assays. Furthermore, RAR?-PLZF recruits HDAC1 and causes histone H3 deacetylation at C/EBP? target loci, thereby decreasing the expression of C/EBP? target genes. In line with these results, HDAC inhibitors restore in part C/EBP? target gene expression. These findings provide molecular evidence for a mechanism through which RAR?-PLZF acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with C/EBP? and inhibiting its activity.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第33期|13522-13527|共6页
作者
Girard N.; Tremblay M.; Humbert M.Grondin B.Haman A.Labrecque J.Chen B.Chen Z.Chen S.-J.Hoang T.;
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作者单位

Institute of Research in Immunology and Cancer (IRIC), Canada;

Clinical Research Institute of Montreal, Montreal, QC, H2W 1R7, Canada;

State Key Laboratory of Medical Genomics, China;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
APL; Granulocyte differentiation; Histone modification; Protein interaction; Transcription inhibition;

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

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