Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-03-08

AUTHORS

M Murai, M Toyota, A Satoh, H Suzuki, K Akino, H Mita, Y Sasaki, T Ishida, L Shen, G Garcia-Manero, J-P J Issa, Y Hinoda, T Tokino, K Imai

ABSTRACT

Hypoxia is a key factor contributing to the progression of human neoplasias and to the development of resistance to chemotherapy. BNIP3 is a proapoptotic member of the Bcl-2 protein family involved in hypoxia-induced cell death. We evaluated the expression and methylation status of BNIP3 gene to better understand the role of epigenetic alteration of its expression in haematopoietic tumours. Methylation of the region around the BNIP3 transcription start site was detected in four acute lymphocytic leukaemia, one multiple myeloma and one Burkitt lymphoma cell lines, and was closely associated with silencing the gene. That expression of BNIP3 was restored by treatment with 5-aza2′-deoxycytidine (5-aza-dC), a methyltransferase inhibitor, which confirmed the gene to be epigenetically inactivated by methylation. Notably, re-expression of BNIP3 using 5-aza2-dC also restored hypoxia-mediated cell death in methylated cell lines. Acetylation of histone H3 in the 5′ region of the gene, which was assessed using chromatin immunoprecipitation assays, correlated directly with gene expression and inversely with DNA methylation. Among primary tumours, methylation of BNIP3 was detected in five of 34 (15%) acute lymphocytic leukaemias, six of 35 (17%) acute myelogenous leukaemias and three of 14 (21%) multiple myelomas. These results suggest that aberrant DNA methylation of the 5′ CpG island and histone deacetylation play key roles in silencing BNIP3 expression in haematopoietic tumours. More... »

PAGES

1165-1172

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6602422

DOI

http://dx.doi.org/10.1038/sj.bjc.6602422

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022760007

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15756280


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31 BNIP3 expression
32 BNIP3 gene
33 Bcl-2 protein family
34 Bnip3 gene expression
35 Burkitt's lymphoma cell lines
36 CpG islands
37 DNA methylation
38 H3
39 aberrant DNA methylation
40 acetylation
41 acute lymphocytic leukemia
42 acute myelogenous leukemia
43 alterations
44 assays
45 cell death
46 cell lines
47 chemotherapy
48 chromatin immunoprecipitation assays
49 deacetylation
50 death
51 development
52 development of resistance
53 epigenetic alterations
54 expression
55 expression of BNIP3
56 factors
57 family
58 gene expression
59 genes
60 haematopoietic tumours
61 histone H3
62 histone deacetylation
63 human neoplasia
64 hypoxia
65 hypoxia-induced cell death
66 immunoprecipitation assays
67 inhibitors
68 islands
69 key factors
70 key role
71 leukemia
72 lines
73 lymphocytic leukemia
74 lymphoma cell lines
75 members
76 methylation
77 methylation of BNIP3
78 methylation status
79 methyltransferase inhibitor
80 multiple myeloma
81 myelogenous leukemia
82 myeloma
83 neoplasia
84 primary tumor
85 proapoptotic member
86 progression
87 protein family
88 region
89 resistance
90 results
91 role
92 sites
93 start site
94 status
95 transcription start site
96 treatment
97 tumors
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