[Genomic distribution of AML1-ETO fusion protein binding sites].
This study was purposed to characterize the genomic distribution of the binding sites for AML1-ETO fusion protein on chromosome 2, 9 and 19, and to further gain insights into the characteristics of transcriptional regulation by AML1-ETO in acute myeloid leukemia so as to provide theoretical basis for the development of targeted therapy and optimization for treatment. Chromatin immunoprecipitation (ChIP) coupled with high density tiling arrays (chip), also known as ChIP-chip, was utilized in this study. ChIP-DNA enriched by an anti-ETO antibody and total genomic DNA of Kasumi cells were hybridized to tiling arrays, tiled through chromosome 2, 9 and 19. The ChIP enriched regions were identified using a model based analytical tool (MAT). Genomic distribution of the ChIP regions was analyzed using publicly available CEAS web server. The Gene Ontology (GO) enrichment analysis was performed to excavated the biological significance. The results indicated that a total of 588 enriched regions were identified on chromosome 2, 9 and 19 by the anti-ETO antibody. A number of the identified regions were located within enhancers (48.86%) or introns (37.35%), much smaller fractions were within proximal promoters (5.96%) or exons (5.49%). Functional enrichment analysis showed that cell proliferation and signal transduction biological pathways were enriched in potential genes of AML-ETO. It is concluded that half of the AML1-ETO binding sites are located within known transcriptional regulatory regions (promoter, 5' UTR and enhancer), while almost another half were within the sequences which were not previously reported as regulatory regions. The potential target molecular network of AML1-ETO is involved in several essential biological processes.
He
Miao-Miao
MM
State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Shi
Jian-Tao
JT
Zhu
Xue-Hua
XH
Jin
Wen
W
Wang
Ping
P
Zhang
Ji
J
Wagn
Kan-Kan
KK
D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein