Bo Zhao (Brigham and Women’s Hospital / Harvard Medical School, USA)
–”NPC Epigenetic Landscapes and Super-Enhancers”
Chromatin modifying enzymes are frequently altered in NPC (Lin D et al Nature Genetics 2014) exome-seq results
Epigenetic changes are reversible and druggable
Super-enhancers are recently discovered enhancers with
(1). Extraordinarily wide and tall signals for H3K27ac, BRD4 etc
(2) critical importance for cell identity, proliferation , renewal, differentiation, and oncogenesis
(3)
(4)
Superenhancer are very cell type-specific?
Alterations in genome structure acquire new super-enhancers epigenetic alterations at CTCG. Zhou et al Cancer Discovery 2016
TAD
Viral super-enhancers
• resting B cells
• EBV infection
• immortalized lymphoblastic cells
The method
H3K27ac ChIP-seq analyses
NP69.
NOK
C666
NPC biopsies. C88T, C128T C15
Control tissue
H3K29ac ChIp-seq signals at the DNMT3A locus
SYK locus (gene body)
Transcription factor motif enriched at the enhancers
NPC panel: NFKB-p65, MYB, IRF1
Controls: enriched in p53, TEAD1, CEBPb).
ETV6
JQ1 treatment inhibits NPC Cell liens growth
(A inhibitor of pTEBb
JQ1 treatment decreases transcription and superenhanvcer-associated gene expression
In the virgenome. ChIP-sea shows superenhancers at
BERER/oriP
Qp-EBNA1
LMP1
Assigning enhancers to their direct targets: HiChIP
Super-enhancers town stream of MYC link to MYC TSS
SLC2A1 links to multiple enhancers
Crisper experiment identify NF-KB and GLUT1 affect
C666 is an excellent cell line and is very similar to primary NPC tumors
Super-enhancer are sensitive to tyrbations