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Image: On the cover: Kanki and Minami et al present a global map of VEGF-mediated dynamic transcriptional events, using ChIP-seq to focus on major histone-coding profiles
.
They discovered a bivalent histone-tagged immediate early transcription factor essential for VEGF-responsive angiogenesis
By systematically analyzing epigenetic changes in vascular endothelial cells stimulated by angiogenesis, Professor Takashi Minami (Kumamoto University, Japan) and his team discovered a unique epigenetic modification (bivalent histone mark switch ), a key transcription factor specific for genes necessary for the induction of angiogenesis, and revealed that histone modifications responsible for this modification are critical for postnatal angiogenesis
.
Although comprehensive epigenetic datasets have been constructed, especially in cancer or stem cell (ES/iPS) cells, the epigenomic dynamics of normal vascular endothelial cells upon angiogenesis stimulation are still not fully understood
.
Dr.
Minami's new research promises to build an epigenomic database for normal endothelial cells and selective epigenomic drug discovery to prevent age-related vascular disease
The network of blood vessels that extends throughout the body is the basis for the biological homeostasis that maintains the body in a stable state
.
Endothelial cells form the basis of these blood vessels, and their normal function is necessary for human health
To address this question, Dr.
Minami and his team performed a genome-wide analysis of epigenetic changes (changes in mRNA and histone modifications) in VEGF (vascular endothelial growth factor necessary for angiogenesis) signaling
.
They then cataloged and mapped those changes to see where the changes occurred
They found that when vascular endothelial cells receive a VEGF signal, a unique 'bivalent histone switch' is triggered, which is restricted to an immediate-early-type transcription factor critical for angiogenesis, and the transcription factor NFAT The timing of the transfer (the transcription factor involved in, among other things, immune responses and cardiac muscle development) into the nucleus
.
The term "bivalent" refers to the coexistence of H3K27me3 (transcriptional brake) and H3K4me3 (transcriptional accelerator) in the region of transcription factor expression
.
H3K4me3 marks epigenetic histone modifications
The researchers also found that endothelial cell-specific depletion of PRC1.
3 and PTIP only inhibited postnatal VEGF-induced angiogenesis without affecting vascular development, thereby delaying cancer growth and suppressing pathological inflammation
.
In recent years, the epigenome has been considered a "chromatin biology" that includes histone modifications and nuclear structure
.
It is currently mainly studied in ES/iPS cells and cancer cells
Dr Minami commented: "We believe that the development of drugs that specifically inhibit the PTIP-NFAT interaction, as well as epigenomic drugs that focus on atypical PRC1.
3, has the potential to lead the way in selective drug discovery to prevent the development of found vascular disease
.
"
article title
Bivalent histone-marked immediate-early gene regulation is vital for VEGF-responsive angiogenesis
