Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells
ABSTRACT
Background Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.
Results To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We identified 3,765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. Notably, reflecting the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing.
Conclusions While the importance of several HOX genes for early vascular development and adult angiogenesis in pathological conditions has been reported, a systematic analysis of the regulation and roles of HOX genes in mature tissue cells has been lacking. These datasets provide a valuable resource for understanding the vascular system and associated diseases.
List of abbreviations
- EC
- Endothelial cells
- S/N
- signal-to-noise ratio
- PCA
- principal component analysis
- Pol II
- RNA Polymerase II
- FDR
- false discovery rate
- GWAS
- Genome-wide association study
- SNP
- single-nucleotide polymorphism
- GO
- Gene Ontology
- DP
- differential promoter
- DE
- differential enhancer
- DEG
- differentially expressed gene
- TAD
- topologically associating domain
- C-DOM
- the centromeric domain
- T-DOM
- the telomeric domain
- vWF
- von Willebrand factor
- TPM
- Transcripts Per Kilobase Million
Subject Area
- Biochemistry (11752)
- Bioengineering (8752)
- Bioinformatics (29200)
- Biophysics (14974)
- Cancer Biology (12096)
- Cell Biology (17411)
- Clinical Trials (138)
- Developmental Biology (9421)
- Ecology (14182)
- Epidemiology (2067)
- Evolutionary Biology (18308)
- Genetics (12245)
- Genomics (16803)
- Immunology (11869)
- Microbiology (28097)
- Molecular Biology (11594)
- Neuroscience (60969)
- Paleontology (451)
- Pathology (1871)
- Pharmacology and Toxicology (3238)
- Physiology (4959)
- Plant Biology (10427)
- Synthetic Biology (2886)
- Systems Biology (7340)
- Zoology (1651)