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Series GSE71671 Query DataSets for GSE71671
Status Public on Aug 04, 2015
Title Inhibition of EZH2 in THP-1 cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation.
Overall design THP-1s were treated with the EZH2 inhibitor GSK126 for phenotypic and genotypic analysis.
Contributor(s) Winkler J, Fox HS
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Submission date Aug 03, 2015
Last update date Jul 26, 2018
Contact name Jessi Winkler
Organization name UNMC
Department Exp Neuroscience and Pharmacology
Street address DRC I
City Omaha
State/province Nebraska
ZIP/Postal code 68198
Country USA
Platforms (1)
GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
Samples (6)
GSM1842691 1 THP 1
GSM1842692 2 THP 1
GSM1842693 3 THP 1
BioProject PRJNA291772

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Supplementary file Size Download File type/resource
GSE71671_RAW.tar 22.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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