Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer

@article{Orouji2021ChromatinSD,
  title={Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer},
  author={Elias Orouji and Ayush T. Raman and Anand K. Singh and Alexey V. Sorokin and Emre Arslan and Archit K. Ghosh and Jonathan Schulz and Christopher J. Terranova and Shan Jiang and Ming Tang and Mayinuer Maitituoheti and S. Carson Callahan and Praveen Barrodia and Katarzyna Tomczak and Yingda Jiang and Zhi-qin Jiang and Jennifer S Davis and Sukhen C Ghosh and Hey Min Lee and Laura Reyes-Uribe and Kyle Chang and Yusha Liu and Huiqin Chen and Ali Azhdarinia and Jeffrey Morris and Eduardo Vilar and Kendra S. Carmon and Scott Kopetz and Kunal Rai},
  journal={Gut},
  year={2021}
}
Objective Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described. Design We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer… Expand

References

SHOWING 1-10 OF 53 REFERENCES
Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome
TLDR
The findings indicate that the CRC epigenome is defined by highly recurrent epigenetic alterations at enhancers which activate a common, aberrant transcriptional programme critical for CRC growth and survival. Expand
Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer
TLDR
Thousands of variant enhancer loci (VELs) are identified that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome that is proposed to drive a specific transcriptional program to promote colon carcinogenesis. Expand
Mismatch repair-signature mutations activate gene enhancers across human colorectal cancer epigenomes
TLDR
It is demonstrated that signature mismatch-repair (MMR) mutations activate enhancers using a xenograft tumor metastasis model, where mutations are induced naturally via CRISPR/Cas9 inactivation of MLH1 prior to tumor cell injection. Expand
DNA Demethylase Activity Maintains Intestinal Cells in an Undifferentiated State Following Loss of APC
TLDR
Loss of the APC tumor suppressor gene causes upregulation of a DNA demethylase system and the concomitant hypomethylation of key intestinal cell fating genes, implying a model wherein APC controls intestinal cellfating through a switch in DNA methylation dynamics. Expand
The chromatin accessibility landscape of primary human cancers
TLDR
These chromatin accessibility profiles identify cancer- and tissue-specific DNA regulatory elements that enable classification of tumor subtypes with newly recognized prognostic importance, and identify distinct TF activities in cancer based on differences in the inferred patterns of TF-DNA interaction and gene expression. Expand
Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
TLDR
This work investigates how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition ofThe MYC oncogene in multiple myeloma (MM), and finds that super-enhancers were found at key oncogenic drivers in many other tumor cells. Expand
Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer
TLDR
It is found that spatial partitioning of the open and closed genome compartments is profoundly compromised in tumors and reorganization is accompanied by compartment-specific hypomethylation and chromatin changes. Expand
Comprehensive molecular characterization of human colon and rectal cancer
TLDR
Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. Expand
BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma.
TLDR
It is found that rather than interacting with transcription cofactors, BRN2 is instead associated with DNA damage response proteins and directly binds PARP1 and Ku70/Ku80, highlighting a novel role for a key transcription factor in reprogramming DNA damage repair and suggesting that BRn2 may impact the response to DNA-damaging agents in BRN1-expressing cancers. Expand
The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression
TLDR
The zinc-finger transcription factor GATA6 is identified as a key regulator of the WNT and BMP pathways in CRC and creates an environment permissive for CRC initiation by lowering the threshold of BMP signalling required for tumour stem cell expansion. Expand
...
1
2
3
4
5
...