Comparison of DNMT1 inhibitors by methylome profiling identifies unique signature of 5-aza-2'deoxycytidine

Sarah-Jayne Mackin, Karla O'Neill, CP Walsh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

AIM: 5-aza-2'deoxycytidine (Aza) is used to treat myelodysplastic syndrome and is in trials for other cancers. It acts chiefly as a hypomethylating agent inhibiting DNMT1. A lack of understanding of off-target effects in normal cells hinders wider usage. MATERIALS & METHODS: We compared treatment of the same normosomic, nontransformed fibroblast cell line with Aza and SMARTpool siRNA against DNMT1. Methylation and transcription were assayed using Illumina 450k and HT12 arrays. RESULTS: Both Aza and DNMT1 siRNA caused overall hypomethylation, with siRNA more efficient at demethylating gene bodies. Hypomethylation at the promoters of many histones, and hypermethylation at multiple sites genome wide, were unique to Aza treatment. CONCLUSION: Aza had important unique effects and targets compared with DNMT1 inhibition via siRNA.
LanguageEnglish
Pages1085-1101
Number of pages16
JournalEpigenomics
Volume10
Issue number8
Early online date31 Jul 2018
DOIs
Publication statusPublished - 2 Aug 2018

Fingerprint

decitabine
Small Interfering RNA
Myelodysplastic Syndromes
Histones
Methylation
Fibroblasts
Genome
Cell Line
Genes

Cite this

@article{2e344f1fd4134480837e84d4913a5bfc,
title = "Comparison of DNMT1 inhibitors by methylome profiling identifies unique signature of 5-aza-2'deoxycytidine",
abstract = "AIM: 5-aza-2'deoxycytidine (Aza) is used to treat myelodysplastic syndrome and is in trials for other cancers. It acts chiefly as a hypomethylating agent inhibiting DNMT1. A lack of understanding of off-target effects in normal cells hinders wider usage. MATERIALS & METHODS: We compared treatment of the same normosomic, nontransformed fibroblast cell line with Aza and SMARTpool siRNA against DNMT1. Methylation and transcription were assayed using Illumina 450k and HT12 arrays. RESULTS: Both Aza and DNMT1 siRNA caused overall hypomethylation, with siRNA more efficient at demethylating gene bodies. Hypomethylation at the promoters of many histones, and hypermethylation at multiple sites genome wide, were unique to Aza treatment. CONCLUSION: Aza had important unique effects and targets compared with DNMT1 inhibition via siRNA.",
author = "Sarah-Jayne Mackin and Karla O'Neill and CP Walsh",
year = "2018",
month = "8",
day = "2",
doi = "10.2217/epi-2017-0171",
language = "English",
volume = "10",
pages = "1085--1101",
journal = "Epigenomics",
issn = "1750-1911",
publisher = "Future Medicine Ltd.",
number = "8",

}

Comparison of DNMT1 inhibitors by methylome profiling identifies unique signature of 5-aza-2'deoxycytidine. / Mackin, Sarah-Jayne; O'Neill, Karla; Walsh, CP.

In: Epigenomics, Vol. 10, No. 8, 02.08.2018, p. 1085-1101.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparison of DNMT1 inhibitors by methylome profiling identifies unique signature of 5-aza-2'deoxycytidine

AU - Mackin, Sarah-Jayne

AU - O'Neill, Karla

AU - Walsh, CP

PY - 2018/8/2

Y1 - 2018/8/2

N2 - AIM: 5-aza-2'deoxycytidine (Aza) is used to treat myelodysplastic syndrome and is in trials for other cancers. It acts chiefly as a hypomethylating agent inhibiting DNMT1. A lack of understanding of off-target effects in normal cells hinders wider usage. MATERIALS & METHODS: We compared treatment of the same normosomic, nontransformed fibroblast cell line with Aza and SMARTpool siRNA against DNMT1. Methylation and transcription were assayed using Illumina 450k and HT12 arrays. RESULTS: Both Aza and DNMT1 siRNA caused overall hypomethylation, with siRNA more efficient at demethylating gene bodies. Hypomethylation at the promoters of many histones, and hypermethylation at multiple sites genome wide, were unique to Aza treatment. CONCLUSION: Aza had important unique effects and targets compared with DNMT1 inhibition via siRNA.

AB - AIM: 5-aza-2'deoxycytidine (Aza) is used to treat myelodysplastic syndrome and is in trials for other cancers. It acts chiefly as a hypomethylating agent inhibiting DNMT1. A lack of understanding of off-target effects in normal cells hinders wider usage. MATERIALS & METHODS: We compared treatment of the same normosomic, nontransformed fibroblast cell line with Aza and SMARTpool siRNA against DNMT1. Methylation and transcription were assayed using Illumina 450k and HT12 arrays. RESULTS: Both Aza and DNMT1 siRNA caused overall hypomethylation, with siRNA more efficient at demethylating gene bodies. Hypomethylation at the promoters of many histones, and hypermethylation at multiple sites genome wide, were unique to Aza treatment. CONCLUSION: Aza had important unique effects and targets compared with DNMT1 inhibition via siRNA.

U2 - 10.2217/epi-2017-0171

DO - 10.2217/epi-2017-0171

M3 - Article

VL - 10

SP - 1085

EP - 1101

JO - Epigenomics

T2 - Epigenomics

JF - Epigenomics

SN - 1750-1911

IS - 8

ER -