NDLI: Deep sequencing reveals novel Set7 networks

Content Provider	Springer Nature Link
Author	Keating, Samuel T. Ziemann, Mark Okabe, Jun Khan, Abdul Waheed Balcerczyk, Aneta El Osta, Assam
Copyright Year	2014
Abstract	Methyl-dependent regulation of transcription has expanded from a traditional focus on histones to encompass transcription factor modulation. While the Set7 lysine methyltransferase is associated with pro-inflammatory gene expression in vascular endothelial cells, genome-wide regulatory roles remain to be investigated. From initial characterization of Set7 as specific for methyl-lysine 4 of H3 histones (H3K4m1), biochemical activity toward non-histone substrates has revealed additional mechanisms of gene regulation.mRNA-Seq revealed transcriptional deregulation of over 8,000 genes in an endothelial model of Set7 knockdown. Gene ontology identified up-regulated pathways involved in developmental processes and extracellular matrix remodeling, whereas pathways regulating the inflammatory response as well as nitric oxide signaling were down-regulated. Chromatin maps derived from ChIP-Seq profiling of H3K4m1 identified several hundred loci with loss of H3K4m1 at gene regulatory elements associated with an unexpectedly subtle effect on gene expression. Transcription factor network analysis implicated six previously described Set7 substrates in mRNA-Seq changes, and we predict that Set7 post-translationally regulates other transcription factors associated with vascular endothelial gene expression through the presence of Set7 amino acid methylation motifs.We describe a role for Set7 in regulating developmental pathways and response to stimuli (inflammation/immune response) in human endothelial cells of vascular origin. Set7-dependent gene expression changes that occurred independent of H3K4m1 may involve transcription factor lysine methylation events. The method of mapping measured transcriptional changes to transcription factors to identify putative substrates with strong associations to functional changes is applicable to substrate prediction for other broad-substrate histone modifiers.
Starting Page	4471
Ending Page	4486
Page Count	16
File Format	PDF
ISSN	1420682X
Journal	Cellular and Molecular Life Sciences
Volume Number	71
Issue Number	22
e-ISSN	14209071
Language	English
Publisher	Springer Basel
Publisher Date	2014-05-30
Publisher Place	Basel
Access Restriction	Subscribed
Subject Keyword	Lysine methylation Set7 ChIP-Seq Transcriptome Substrate prediction STAT1 Cell Biology Biomedicine general Life Sciences Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience

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