Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD-dependent gene expression.

Abstract:

:Gene promoters are enriched in guanine clusters that potentially fold into quadruplex structures. Such quadruplexes were implicated in the regulation of gene expression, plausibly by interacting with transcription factors. We showed previously that homodimers of the myogenic transcription factor MyoD bound in vitro most tightly bimolecular quadruplexes of promoter sequences of muscle-specific genes. By contrast, MyoD-E47 heterodimers formed tighter complexes with d(CANNTG) E-box motifs that govern muscle gene expression. Here, we show that DNA quadruplexes enhance in vivo MyoD and E-box-driven expression of a firefly luciferase (FL) reporter gene. HEK293 cells were transfected with FL expressing p4RTK-FL vector alone or together with MyoD expressing pEMSV-MyoD plasmid, with quadruplexes of alpha7 integrin or sarcomeric mitochondrial creatine kinase (sMtCK) muscle gene promoters or with a combination thereof. Whereas MyoD elevated by approximately 10-fold the levels of FL mRNA and protein, the DNA quadruplexes by themselves did not affect FL expression. However, together with MyoD, quadruplex DNA increased by approximately 35-fold the amounts of FL mRNA and protein. Without affecting its expression, DNA quadruplexes bound MyoD in the cells. Based on these results, we propose models for the regulation of muscle gene transcription by direct interaction of MyoD with promoter quadruplex structures.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Shklover J,Weisman-Shomer P,Yafe A,Fry M

doi

10.1093/nar/gkp1208

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

2369-77

issue

7

eissn

0305-1048

issn

1362-4962

pii

gkp1208

journal_volume

38

pub_type

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