In this section
@article{Antariksa:2024:10.1021/acs.accounts.4c00574,
author = {Antariksa, NF and Di, Antonio M},
doi = {10.1021/acs.accounts.4c00574},
journal = {Accounts of Chemical Research},
pages = {3397--3406},
title = {The emerging roles of multimolecular G-quadruplexes in transcriptional regulation and chromatin organization},
url = {http://dx.doi.org/10.1021/acs.accounts.4c00574},
volume = {57},
year = {2024}
}
TY - JOUR
AB - ConspectusThe ability of genomic DNA to adopt non-canonical secondary structures known as G-quadruplexes (G4s) under physiological conditions has been recognized for its potential regulatory function of various biological processes. Among those, transcription has recently emerged as a key process that can be heavily affected by G4 formation, particularly when these structures form at gene promoters. While the presence of G4s within gene promoters has been traditionally associated with transcriptional inhibition, in a model whereby G4s act as roadblocks to polymerase elongation, recent genomics experiments have revealed that the regulatory role of G4s in transcription is more complex than initially anticipated. Indeed, earlier studies linking G4-formation and transcription mainly relied on small-molecule ligands to stabilize and promote G4s, which might lead to disruption of protein–DNA interactions and local environments and, therefore, does not necessarily reflect the endogenous function of G4s at gene promoters. There is now strong evidence pointing toward G4s being associated with transcriptional enhancement, rather than repression, through multifaceted mechanisms such as recruitment of key transcriptional proteins, molding of chromatin architecture, and mode of phase separation.In this Account, we explore pivotal findings from our research on a particular subset of G4s, namely, those formed through interactions between distant genomic locations or independent nucleic acid strands, referred to as multimolecular G4s (mG4s), and discuss their active role in transcriptional regulation. We present our recent studies suggesting that the formation of mG4s may positively regulate transcription by inducing phase-separation and selectively recruiting chromatin-remodeling proteins. Our work highlighted how mG4-forming DNA and RNA sequences can lead to liquid–liquid phase separation (LLPS) in the absence of any protein. This discovery provided new insights into
AU - Antariksa,NF
AU - Di,Antonio M
DO - 10.1021/acs.accounts.4c00574
EP - 3406
PY - 2024///
SN - 0001-4842
SP - 3397
TI - The emerging roles of multimolecular G-quadruplexes in transcriptional regulation and chromatin organization
T2 - Accounts of Chemical Research
UR - http://dx.doi.org/10.1021/acs.accounts.4c00574
VL - 57
ER -