Page 72 - ITPS-7-3

INNOSC Theranostics

and Pharmacological Sciences

REVIEW ARTICLE
Enhancers and super-enhancers as master

regulators in cancer

Pouya Sarvari * , Pourya Sarvari 1† , Ivonne Ramirez-Diaz , and Karla Rubio 2
2
1†
1 Iran’s National Elite Foundation, Tehran, Iran
2 International Laboratory EPIGEN-CONCYTEP-BUAP; Puebla, Mexico

Abstract

Gene expression regulation is one of the most fundamental cellular processes,
enabling the activation of a gene to produce either the translatable protein-coding
transcript (mRNA) or a functional non-coding RNA with gene regulatory functions,
ultimately determining cell identity and function. Although gene expression
regulation can occur at transcriptional, translational, and post-translational levels,
transcription initiation is the first and the most important step in gene expression,
facilitating the transfer of biological information from DNA to protein. Enhancers
and super-enhancers are among the master regulators of tissue- and cell-specific
transcription regulation involved in cell differentiation and tumor formation.
Despite four decades passing since the first discovery of enhancers in eukaryotes
and extensive efforts undertaken to identify enhancers on a genomic scale during the
† These authors contributed equally last decade, the discovery of enhancers still faces certain limitations and needs further
to this work. investigation. The perturbation of enhancer function due to genetic or epigenetic
*Corresponding author: changes is closely linked to a range of human disorders, including the development
Pouya Sarvari and progression of cancers. Thus, the detection of early cancer-related enhancer
(pouya.sarvari2008@gmail.com) activity and the subsequent normalization of expression abnormalities using enhancer-
Citation: Sarvari P, Sarvari P, targeting CRISPR epigenetic editing, as well as enhancer-targeting pharmaceuticals,
Ramirez-Diaz I, Rubio K. Enhancers are regarded as groundbreaking therapeutic tactics in preclinical stages.
and super-enhancers as master
regulators in cancer. INNOSC
Theranostics and Pharmacological
Sciences. 2024;7(3):3654. Keywords: CRISPR; Epigenetic editing; Enhancer-promoter loop; Enhancer-targeting
doi: 10.36922/itps.3654 drugs; Non-coding transcript; Super-enhancers; Transcription
Received: May 13, 2024
Accepted: July 12, 2024
Published Online: July 24, 2024 1. Introduction
Copyright: © 2024 This Enhancers are non-coding regions of DNA, ranging from 200 to 2,000 base pairs in
is an Open-Access article length that can be bound by transcription factors (TFs) to modulate the transcription
distributed under the terms
of the Creative Commons of cell-specific genes. Importantly, the action of enhancers on gene expression is not
AttributionNoncommercial License, restricted by their position or distance from the target gene. Interestingly, enhancers
permitting all non-commercial use, can be located upstream, downstream, adjacent to promoters, or even up to one million
distribution, and reproduction in any
1
medium, provided the original work base pairs away from the target gene. Regardless of their distance, distal enhancers can
is properly cited. form an enhancer-promoter loop complex to physically interact with the promoter of a
Publisher’s Note: AccScience target gene. Enhancers typically contain specific DNA elements recognized by tissue-
Publishing remains neutral with specific TFs. Research has shown that enhancers recruit transcription complexes at the
regard to jurisdictional claims in
published maps and institutional enhancer-promoter loop, including cell-specific TFs such as OCT4, SOX2, KLF4, and
affiliations Nanog, RNA polymerase II (RNA pol II), co-activators, the mediator complex, enhancer

Volume 7 Issue 3 (2024) 1 doi: 10.36922/itps.3654