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Series GSE139678 Query DataSets for GSE139678
Status Public on Sep 03, 2020
Title Hypoxia-mediated regulation of histone demethylases affects angiogenesis associated functions in endothelial cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Purpose: Jumonji-containing (jmjC) family of proteins are involved in epigenetic gene regulation through histone specific lysine demethylation. Previous studies have demonstrated that the expression of several members of this family is induced by hypoxia. However, the mechanisms by which lysine specific demethylases (KDMs) are regulated under hypoxia and how they affect angiogenesis, the primary method to restore blood oxygen, remains unknown. In this study, we characterized regulation of KDMs using a combination of nascent and mature mRNA profiling. Furthermore, we aimed to identify KDMs that play a role in mediating the VEGF-mediated angiogenic response in endothelial cells.
Results: We demonstrated that majority of KDMs were induced by hypoxia and this effect is more prominent upon constitutive activation of HIF2α compared to HIF1α. Half of the changes in mRNAs levels were attributed to transcriptional regulation as evidenced by similar changes at the level of nascent mRNAs, whereas half was likely due to post-transcriptional mechanisms affecting mature mRNA levels. Hypoxia induced genome-wide redistribution of H3K27me3 at 2000 transcriptionally active loci in human umbilical vein endothelial cells (HUVECs). Among these, we further verified the induction of VEGF-A by demethylation of the locus by KDM4B and KDM6B in response to hypoxia. Accordingly, knockdown of KDM4B and KDM6B led to decreased proliferation and tube formation of HUVECs.
Conclusions: Hypoxia leads to both transcriptional and post-transcriptional induction of KDMs and wide redistribution of H3K27me3 at active chromatin regions. Main mediator of angiogenesis, VEGFA, is regulated by KDM4B- and KDM6B- mediated demethylation in HUVECs with functional implications for cell proliferation and tube formation. These findings provide novel insights into the regulation of KDMs by hypoxia and the epigenetic regulation of angiogenesis.
 
Overall design Examination of KDM expressions profiling and H3K27me3 modification near angiogenesis-related genes by KDMs in human umbilical vein endothelial cell (HUVEC).
 
Contributor(s) Liu OH, Kaikkonen MU
Citation(s) 32938217
Submission date Oct 31, 2019
Last update date Dec 07, 2020
Contact name Oscar Hsin-Fu Liu
E-mail(s) oscar.liu@uef.fi
Organization name University of Eastern Finland
Department Department of Biotechnology and Molecular Medicine
Lab A.I.Virtanen Institute for Molecular Sciences
Street address P.O.Box 1627 (Neulaniementie 2)
City Kuopio
State/province Finland
ZIP/Postal code 70211
Country Finland
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (24)
GSM4145952 RNASeq_HUVEC_siCTL_Nox_rep1
GSM4145953 RNASeq_HUVEC_siKDM4B_Nox_rep1
GSM4145954 RNASeq_HUVEC_siKDM6B_Nox_rep1
Relations
BioProject PRJNA586868
SRA SRP227843

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE139678_Gene_expression_RPKM.txt.gz 3.2 Mb (ftp)(http) TXT
GSE139678_RAW.tar 2.1 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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