YY1 interacts with guanine quadruplexes to regulate DNA looping and gene expression

Abstract

Summary The DNA guanine quadruplexes (G4) play important roles in multiple cellular processes, including DNA replication, transcription and maintenance of genome stability. Here, we showed that Yin Yang-1 (YY1) can bind directly to G4 structures. ChIP-Seq results revealed that YY1 binding sites overlap extensively with G4 structure loci in chromatin. We also observed that YY1’s dimerization and its binding with G4 structures contribute to YY1-mediated long-range DNA looping. Displacement of YY1 from G4 structure sites disrupts substantially the YY1-mediated DNA looping. Moreover, treatment with G4-stabilizing ligands modulates the expression of not only those genes with G4 structures in their promoters, but also those associated with distal G4 structures that are brought to close proximity via YY1-mediated DNA looping. Together, we identified YY1 as a novel DNA G4-binding protein, and revealed that YY1-mediated long-range DNA looping requires its dimerization and occurs, in part, through its recognition of G4 structure.

Mechanisms of Enhancer-Promoter Interactions in Higher Eukaryotes

“…According to the proposed model, YY1 forms homodimers, which can bring the associated gene enhancers and promoters closer together. A cluster of C2H2 domains and an adjacent unstructured domain are responsible for the dimerization and oligomerization of YY1 [ 103 , 104 ]. Moreover, the dimerization and subsequent oligomerization of YY1 results in non-specific binding to DNA, especially with guanine quadruplexes (G4).…”

“…Moreover, the dimerization and subsequent oligomerization of YY1 results in non-specific binding to DNA, especially with guanine quadruplexes (G4). Some experimental evidence has suggested that the dimerization of YY1 and the subsequent binding to G4 structures contribute to the YY1-mediated formation of long DNA loops [ 104 ]. YY1 may also participate in the organization of distance interactions through the regulation of proteins that are directly involved in the formation of chromatin loops.…”

Mechanisms of Enhancer-Promoter Interactions in Higher Eukaryotes

“…According to the proposed model, YY1 forms homodimers, which can bring the associated gene enhancers and promoters closer together. A cluster of C2H2 domains and an adjacent unstructured domain are responsible for the dimerization and oligomerization of YY1 [90,91]. Moreover, the dimerization and subsequent oligomerization of YY1 results in non-specific binding to DNA, especially with guanine quadruplexes (G4).…”

“…Moreover, the dimerization and subsequent oligomerization of YY1 results in non-specific binding to DNA, especially with guanine quadruplexes (G4). Some experimental evidence has suggested that the dimerization of YY1 and the subsequent binding to G4 structures contribute to the YY1-mediated formation of long DNA loops [91]. YY1 may also participate in the organization of distance interactions through the regulation of proteins that are directly involved in the formation of chromatin loops.…”

Vimentin binds to G-quadruplex repeats found at telomeres and gene promoters

“…In this regard, accumulating evidence suggests that, at accessible chromatin regions, 10 DNA folding into non-canonical structures may drive the recruitment of architectural proteins to promote gene clustering. 11,12 Among all DNA non-canonical secondary structures, G-quadruplexes (G4s) are tetra-helical arrangements that form within guanine-rich tracts. Here, four guanines interact through Hoogsteen hydrogen bonds to form planar arrays (G-tetrads) that stack one upon the other, building the core of the structure.…”