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Series GSE40440 Query DataSets for GSE40440
Status Public on Jun 25, 2013
Title Histone Demethylase Lsd1 is Required to Repress Hematopoietic Stem and Progenitor Cell Signatures During Blood Cell Maturation
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Here we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis in primary hematopoietic cells, combining global occupancy of Lsd1, genome-wide analysis of its histone substrates H3K4 mono- and di-methylation and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 function was not restricted to transcription start sites, but is also critical at enhancers. Loss of Lsd1 at these sites was associated with increased H3K4me1 and H3K4me2 methylation levels on HSPC genes and their derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells and mature blood cell lineages. Our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation.
Overall design To identify direct target genes of Lsd1 in myeloid cells we mapped global occupancy of Lsd1 in 32D granuolocytic progenitor cells and compared H3K4me1/me2/me3 and H3K27ac histone modifications in Lsd1fl/fl (wild type) vs. Lsd1fl/f Mx1Cre (knockout) Gr1dim Mac1 granuolocytic progenitor cells.
Contributor(s) Kerenyi MA, Orkin SH
Citation(s) 23795291
Submission date Aug 28, 2012
Last update date May 15, 2019
Contact name Marc A. Kerenyi
Organization name Boston Children's Hospital and Dana Farber Cancer Institute
Department Hematology / Oncology
Lab Stuart Orkin Laboratory
Street address 1 Blackfan Street - Karp Research Building
City Boston
State/province Massachusetts
ZIP/Postal code 02115
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL14759 Helicos HeliScope (Mus musculus)
Samples (14)
GSM994230 H3K4me1_Gr1dim_WT
GSM994231 H3K4me1_Gr1dim_Lsd1_KO
GSM994232 H3K4me2_Gr1dim_WT
SRA SRP015343
BioProject PRJNA174296

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Supplementary file Size Download File type/resource
GSE40440_RAW.tar 16.4 Gb (http)(custom) TAR (of BED, WIG)
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Processed data provided as supplementary file
Raw data are available in SRA

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