Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.

Tsompana M, Gluck C, Sethi I, Joshi I, Bard J, Nowak NJ, Sinha S, Buck MJ

Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC are lacking due to the inherent heterogeneity and complexity of the disease. Herein, we have generated the global histone mark based epigenomic and transcriptomic cartogram of SCC25, a representative cell type of mesenchymal HNSCC and its normal oral keratinocyte counterpart. Examination of genomic regions marked by differential chromatin states and associated with misregulated gene expression led us to identify SCC25 enriched regulatory sequences and transcription factors (TF) motifs. These findings were further strengthened by ATAC-seq based open chromatin and TF footprint analysis which unearthed Krüppel-like Factor 4 (KLF4) as a potential key regulator of the SCC25 cistrome. We reaffirm the results obtained from in silico and chromatin studies in SCC25 by ChIP-seq of KLF4 and identify ΔNp63 as a co-oncogenic driver of the cancer-specific gene expression milieu. Taken together, our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of HNSCC by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.

Tags
Antibody
IP-Star Compact

Share this article
Tweet

Published
September, 2019

Source

Products used in this publication

C15410196

H3K27ac Antibody - ChIP-seq Grade
C15410195

H3K27me3 Antibody - ChIP-seq Grade
C15410192

H3K36me3 Antibody - ChIP-seq Grade
C15410194

H3K4me1 Antibody - ChIP-seq Grade
C15410003

H3K4me3 Antibody - ChIP-seq Grade

Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.

Products used in this publication

H3K27ac Antibody - ChIP-seq Grade

H3K27me3 Antibody - ChIP-seq Grade

H3K36me3 Antibody - ChIP-seq Grade

H3K4me1 Antibody - ChIP-seq Grade

H3K4me3 Antibody - ChIP-seq Grade

活动