Universität zu Köln

Spiegel, Jochen ORCID: 0000-0001-7641-1066, Cuesta, Sergio Martinez, Adhikari, Santosh ORCID: 0000-0002-1501-2106, Hansel-Hertsch, Robert, Tannahill, David and Balasubramanian, Shankar (2021). G-quadruplexes are transcription factor binding hubs in human chromatin. Genome Biol., 22 (1). LONDON: BMC. ISSN 1474-760X

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Abstract

Background The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. Results Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes. Conclusions Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Spiegel, Jochen UNSPECIFIED orcid.org/0000-0001-7641-1066 UNSPECIFIED Cuesta, Sergio Martinez UNSPECIFIED UNSPECIFIED UNSPECIFIED Adhikari, Santosh UNSPECIFIED orcid.org/0000-0002-1501-2106 UNSPECIFIED Hansel-Hertsch, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Tannahill, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Balasubramanian, Shankar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586664
DOI:	10.1186/s13059-021-02324-z
Journal or Publication Title:	Genome Biol.
Volume:	22
Number:	1
Date:	2021
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1474-760X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLECULAR SWITCH; DNA SHAPE; RECOGNITION; MOTIF; VISUALIZATION; ALTERS; RNA Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58666