Systematic name M15068
Brief description Genes whose CpG islands showed greatly increased histone H4 acetylation in NB4 cells (acute promyelocytic leukemia, APL) upon treatment with tretinoin [PubChem=444795].
Full description or abstract Dysregulation of epigenetic control is an important participant in carcinogenesis. The PML/RAR alpha translocation in acute promyelocytic leukemia (APL) is an example where the resultant fusion protein recruits histone deacetylase complexes to target genes resulting in their inappropriate transcriptional repression. All-trans-retinoic acid (ATRA) acts as a ligand that relieves this repression and produces an epigenetic transcriptional reprogramming of the cancer cell. CpG island microarrays were used to analyze the DNA methylation and histone acetylation state of the human APL cell line NB4 before and after differentiation with ATRA as well as normal peripheral blood mononuclear cells (PBMC). Over 70 CpG islands within 1 kb of transcription start of a known gene are aberrantly methylated in NB4 cells compared with PBMC; however, no changes in cytosine methylation were detected following ATRA-induced differentiation. With respect to histone H4 acetylation, over 100 single-copy CpG islands within 1 kb of transcription start of a known human gene became hyperacetylated following ATRA-induced differentiation. One CpG island was aberrantly methylated in NB4 cells, but became hyperacetylated and was induced following ATRA treatment and was associated with the HoxA1 gene, suggesting it may be a target gene of ATRA in APL. In addition to single-copy sequences, a selective increase in acetylation was detected in satellite DNA when compared with other high-copy sequences, such as Alu or rDNA. In summary, ATRA stimulates complex epigenomic changes during leukemic cell differentiation, and monitoring these changes may help to identify new targets of epigenetic dysfunction.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15302897   Authors: Nouzova M,Holtan N,Oshiro MM,Isett RB,Munoz-Rodriguez JL,List AF,Narro ML,Miller SJ,Merchant NC,Futscher BW
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Source species Homo sapiens
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Version history 3.0: Renamed from NOUZOVA_CPG_H4_UP

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