The epigenome of AML stem and progenitor cells.
Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSCs or cancer-initiating cell). The mechanisms underlying switches from CSCs to non-CSCs in vivo remain to be understood. We address this issue in AML from the aspect of epigenetics using genome-wide screening for DNA methylation and selected histone modifications. We found no major differences in DNA methylation, especially in promoter CpG islands, between CSCs and non-CSCs. By contrast, we found thousands of genes that change H3K4me3 and/or H3K27me3 status between stem and progenitor cells as well as between progenitor and mature cells. Stem cell related pathways and proliferation or metabolism related pathways characterize genes differentially enriched for H3K4me3/H3K27me3 in stem and progenitor populations. Bivalent genes in stem cells are more plastic during differentiation and are more likely to lose H3K4me3 than to lose H3K27me3, consistent with increasingly closed chromatin state with differentiation. Our data indicates that histone modifications but not promoter DNA methylation are involved in switches from CSCs to non-CSCs in AML.
['Yamazaki|Jumpei|J|', 'Estecio|Marcos R|MR|', 'Lu|Yue|Y|', 'Long|Hai|H|', 'Malouf|Gabriel G|GG|', 'Graber|David|D|', 'Huo|Yujia|Y|', 'Ramagli|Louis|L|', 'Liang|Shoudan|S|', 'Kornblau|Steven M|SM|', 'Jelinek|Jaroslav|J|', 'Issa|Jean-Pierre J|JP|']
D002454:Cell Differentiation D002843:Chromatin D047369:Chromatin Immunoprecipitation D018899:CpG Islands D019175:DNA Methylation D044127:Epigenesis, Genetic D015973:Gene Expression Regulation, Leukemic D006657:Histones D006801:Humans D015470:Leukemia, Myeloid, Acute D014411:Neoplastic Stem Cells D020411:Oligonucleotide Array Sequence Analysis D011499:Protein Processing, Post-Translational D017422:Sequence Analysis, DNA D015398:Signal Transduction
AML stem progenitor DNA methylation histone modification