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Genome‐wide mapping of large organized heterochromatin domains reveals hotspots of epigenetic and transcriptional changes associated with myeloid differentiation and acute myeloid leukemia (565.1)
Author(s) -
Grigoryev Sergei,
Salzberg Anna,
Berg Arthur,
HarrisBecker Abigail,
Loughran Thomas,
Claxton David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.565.1
Subject(s) - epigenetics , epigenomics , biology , myeloid leukemia , dna methylation , histone , chromatin , genetics , histone h3 , cancer research , computational biology , gene , gene expression
Acute myeloid leukemia (AML) is a highly malignant blood cancer with the lowest survival rate among the four major types of leukemia. The objective of this study was to conduct a genome‐wide mapping of the epigenetic states in the normal myeloid and leukemia cells and to identify the chromosomal domains undergoing epigenetic and transcriptional destabilization. We hypothesized that large‐scale epigenetic changes manifested by heterochromatin markers, histone H3 di‐ and tri‐methylation at lysine 9, may interfere with transcription and promote AML. We used ChIP‐sequencing to conduct a detailed whole‐genomic characterization of H3(K9) methylation. For this study, we used primary AML myeloblasts, normal granulocytes, CD34+ hematopoietic progenitors, and cultured K562 cells as an epigenomic reference. Using ChIP‐sequencing, we mapped genome‐wide topography of histone H3(K9) methylation and its transitions in the process of myeloid differentiation and characterized spatial and functional relationship between histone H3(K9) methylation and transcriptional changes in AML. Aided by application of genome‐wide bioinformatic analysis using a hidden Markov model we were able to reveal multiple associations of chromatin modification topographies with transcription in leukemia and specific chromosomal domains undergoing both epigenetic and transcriptional changes. We expect that the observed epigenomic transitions may serve for AML prognosis as well as targets for its epigenetic therapy. Grant Funding Source : Supported by Pennsylvania Department of Health