tailieunhanh - báo cáo khoa học: "Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài:Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin | Jiang et al. Journal of Hematology Oncology 2010 3 48 http content 3 1 48 JOURNAL OF HEMATOLOGY ONCOLOGY RESEARCH Open Access Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin 1 1 1 2 t- 71 1 3 Shaohong Jiang Xudong Ma Yiqun Huang Yunlu Xu Ruiji Zheng Jen-Wei Chiao Abstract Background We have previously demonstrated that phenylhexyl isothiocyanate PHI a synthetic isothiocyanate inhibits histone deacetylases and remodels chromatins to induce growth arrest in HL-60 myeloid leukemia cells in a concentration-dependent manner. Methods To investigate the effect of PHI a novel histone deacetylases inhibitor HDACi on demethylation and activation of transcription of p15 in acute lymphoid leukemia cell line Molt-4 and to further decipher the potential mechanism of demethylation DNA sequencing and modified methylation specific PCR MSP were used to screen p15-M and p15-U mRNA after Molt-4 cells were treated with PHI 5-Aza and TSA. DNA methyltransferase 1 DNMT1 3A DNMT3A 3B DNMT3B and p15 mRNA were measured by RT-PCR. P15 protein acetylated histone H3 and histone H4 were detected by Western Blot. Results The gene p15 in Molt-4 cells was hypermethylated and inactive. Hypermethylation of gene p15 was attenuated and p15 gene was activated de novo after 5 days exposure to PHI in a concentration-dependent manner. DNMT1 and DNMT3B were inhibited by PHI P . Alteration of DNMT3A was not significant at those concentrations. Acetylated histone H3 and histone H4 were accumulated markedly after exposure to PHI. Conclusion PHI could induce both DNA demethylation and acetylated H3 and H4 accumulation in Molt-4 cells. Hypermethylation of gene p15 was reversed and p15 transcription could be reactivated de novo by PHI. Background The major epigenetic transcriptional controls involved in gene silencing are DNA methylation and covalent modification of histone proteins. .