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Status |
Public on Nov 01, 2024 |
Title |
Histone Methylation Patterns in Acute Leukemias are Defined by Genotype Independent of the Disease Phenotype |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Third-party reanalysis
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Summary |
Epigenetic mechanisms, including acetylation, phosphorylation, and methylation of nucleosomal histones, contribute greatly to physiological control of gene expression required for hematopoietic cell differentiation. Perturbations in histone methylation patterns and mutations in histone methyltransferases and demethylases are frequently identified in acute lymphoid and myeloid leukemia. Histone H3 methylation patterns on lysine 4 and 27 residues define bivalent, or poised, chromatin in the embryonic and hematopoietic stem cells. We examined how the bivalent histone methylation patterns change through differentiation from an embryonic stem cell to a hematopoietic stem cell, and followed these changes through malignant lymphoid and myeloid hematopoiesis. Using an integrative bioinformatics analysis of genome-wide histone methylation patterns, we find that a common bivalent histone methylation pattern does not exist for lymphoid or myeloid leukemia. Instead, a select subset of key hematopoietic genes retains the activating H3K4 trimethyl mark in leukemia cells when compared with hematopoietic stem cells. A close examination of genes marked for active transcription suggests that the malignant transcriptional program is dictated primarily by the cytogenetics and the mutations present in leukemia subtypes. Our findings have implications in determining the treatment for leukemia using epigenetic inhibitors, particularly for those malignancies with a mixed immunophenotype.
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Overall design |
ChIP-seq, 2 biological pulldown replicates and 1 input control for 2 cell lines. Re-processed data for hESC cell lins, CD34+ donor samples, Kasumi1, and DOHH2 were downloaded from sources detailed in public_data_sources.csv.
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Contributor(s) |
Heath JL, Boyd JR |
Citation missing |
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Submission date |
Nov 05, 2019 |
Last update date |
Nov 01, 2024 |
Contact name |
Jonathan AR Gordon |
E-mail(s) |
Jonathan.A.Gordon@uvm.edu
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Organization name |
University of Vermont
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Department |
Biochemistry
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Street address |
89 Beaumont Ave Given E209
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City |
Burlington |
State/province |
VT |
ZIP/Postal code |
05405 |
Country |
USA |
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Platforms (1) |
GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
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Samples (10)
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Relations |
Reanalysis of |
GSM773046 |
Reanalysis of |
GSM621404 |
Reanalysis of |
GSM773048 |
Reanalysis of |
GSM621664 |
Reanalysis of |
GSM772951 |
Reanalysis of |
GSM621665 |
Reanalysis of |
GSM621689 |
Reanalysis of |
GSM772950 |
Reanalysis of |
GSM621431 |
Reanalysis of |
GSM621439 |
Reanalysis of |
GSM621414 |
Reanalysis of |
GSM773047 |
Reanalysis of |
GSM773041 |
Reanalysis of |
GSM773045 |
Reanalysis of |
GSM433179 |
Reanalysis of |
GSM466734 |
Reanalysis of |
GSM469971 |
Reanalysis of |
GSM537626 |
Reanalysis of |
GSM537627 |
Reanalysis of |
GSM537647 |
Reanalysis of |
GSM537648 |
Reanalysis of |
GSM537665 |
Reanalysis of |
GSM537681 |
Reanalysis of |
GSM537683 |
Reanalysis of |
GSM605308 |
Reanalysis of |
GSM605315 |
Reanalysis of |
GSM605335 |
Reanalysis of |
GSM605339 |
Reanalysis of |
GSM621386 |
Reanalysis of |
GSM669887 |
Reanalysis of |
GSM669888 |
Reanalysis of |
GSM669889 |
Reanalysis of |
GSM669893 |
Reanalysis of |
GSM669895 |
Reanalysis of |
GSM669897 |
Reanalysis of |
GSM669936 |
Reanalysis of |
GSM669942 |
Reanalysis of |
GSM669967 |
Reanalysis of |
GSM669974 |
Reanalysis of |
GSM772750 |
Reanalysis of |
GSM772752 |
Reanalysis of |
GSM772754 |
Reanalysis of |
GSM772755 |
Reanalysis of |
GSM772766 |
Reanalysis of |
GSM772794 |
Reanalysis of |
GSM772797 |
Reanalysis of |
GSM772807 |
Reanalysis of |
GSM1534445 |
Reanalysis of |
GSM1534446 |
Reanalysis of |
GSM1534447 |
Reanalysis of |
GSM2308590 |
Reanalysis of |
GSM2308591 |
Reanalysis of |
GSM2308501 |
Reanalysis of |
GSM2308502 |
Reanalysis of |
GSM2308451 |
Reanalysis of |
GSM2308452 |
BioProject |
PRJNA587783 |
SRA |
SRP228612 |
Supplementary file |
Size |
Download |
File type/resource |
GSE139985_CD34-01517_H3K27me3_pooled_FE.bw |
221.2 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01517_H3K4me3_pooled_FE.bw |
112.7 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01536_H3K27me3_pooled_FE.bw |
560.6 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01536_H3K4me3_pooled_FE.bw |
377.9 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01549_H3K27me3_pooled_FE.bw |
346.4 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01549_H3K4me3_pooled_FE.bw |
206.3 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01562_H3K27me3_pooled_FE.bw |
599.8 Mb |
(ftp)(http) |
BW |
GSE139985_CD34-01562_H3K4me3_pooled_FE.bw |
345.0 Mb |
(ftp)(http) |
BW |
GSE139985_DOHH2_H3K27me3_pooled_FE.bw |
1.3 Gb |
(ftp)(http) |
BW |
GSE139985_DOHH2_H3K4me3_pooled_FE.bw |
800.9 Mb |
(ftp)(http) |
BW |
GSE139985_ESH1_H3K27me3_pooled_FE.bw |
554.9 Mb |
(ftp)(http) |
BW |
GSE139985_ESH1_H3K4me3_pooled_FE.bw |
543.6 Mb |
(ftp)(http) |
BW |
GSE139985_ESI3_H3K27me3_pooled_FE.bw |
481.8 Mb |
(ftp)(http) |
BW |
GSE139985_ESI3_H3K4me3_pooled_FE.bw |
463.1 Mb |
(ftp)(http) |
BW |
GSE139985_H3K27ME3_broadPeak.tar.gz |
6.8 Mb |
(ftp)(http) |
TAR |
GSE139985_H3K4ME3_narrowPeak.tar.gz |
13.3 Mb |
(ftp)(http) |
TAR |
GSE139985_HUES48_H3K27me3_pooled_FE.bw |
1001.7 Mb |
(ftp)(http) |
BW |
GSE139985_HUES48_H3K4me3_pooled_FE.bw |
899.7 Mb |
(ftp)(http) |
BW |
GSE139985_HUES64_H3K27me3_pooled_FE.bw |
935.9 Mb |
(ftp)(http) |
BW |
GSE139985_HUES64_H3K4me3_pooled_FE.bw |
756.3 Mb |
(ftp)(http) |
BW |
GSE139985_HUES6_H3K27me3_pooled_FE.bw |
991.2 Mb |
(ftp)(http) |
BW |
GSE139985_HUES6_H3K4me3_pooled_FE.bw |
781.9 Mb |
(ftp)(http) |
BW |
GSE139985_Kasumi1_H3K27me3_pooled_FE.bw |
381.8 Mb |
(ftp)(http) |
BW |
GSE139985_Kasumi1_H3K4me3_pooled_FE.bw |
218.7 Mb |
(ftp)(http) |
BW |
GSE139985_Nalm6_H3K27me3_pooled_FE.bw |
636.6 Mb |
(ftp)(http) |
BW |
GSE139985_Nalm6_H3K4me3_pooled_FE.bw |
514.2 Mb |
(ftp)(http) |
BW |
GSE139985_U937_H3K27me3_pooled_FE.bw |
886.6 Mb |
(ftp)(http) |
BW |
GSE139985_U937_H3K4me3_pooled_FE.bw |
337.1 Mb |
(ftp)(http) |
BW |
GSE139985_public_data_sources.csv.gz |
826 b |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |