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Thermodynamics of i-tetraplex formation in the nuclease hypersensitive element of human c-myc promoter.

Abstract：

:More than 85% of c-myc transcription is controlled by the nuclease hypersensitive element III(1) upstream of the P1 promoter of this oncogene. The purine-rich sequence in the anti-sense strand forms a G-quadruplex, which has been recently implicated in colorectal cancer, and is proposed as a silencer element [Proc. Natl. Acad. Sci. USA 101 (2004) 6140]. This prompted us to characterize the thermodynamics and proton/counterion effect of the complementary pyrimidine-rich sequence, which forms a C-tetraplex. We report the thermodynamic parameters for folding of the pyrimidine-rich DNA fragment from this region into a C-tetraplex. At 20 degrees C, we observed a DeltaG of -10.36+/-0.13kcalmol(-1) with favorable enthalpy (DeltaH=75.99+/-0.99kcalmol(-1)) and unfavorable entropy (TDeltaS=65.63+/-0.88 kcalmol(-1)) at pH 5.3 in 20mM NaCl for tetraplex folding. Similar characteristic stabilizing enthalpy and destabilizing entropy were observed at other pH and ionic strengths. Folding was induced by uptake of about two to three protons per mole of tetraplex while a marginal (0.5-1mol/mol) counterion uptake was observed. In the context of current understanding of c-myc transcription we envisage a role of the i-motif in remodeling the G-quadruplex silencer.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Mathur V,Verma A,Maiti S,Chowdhury S

doi

10.1016/j.bbrc.2004.06.074

subject

Has Abstract

pub_date

2004-08-06 00:00:00

pages

1220-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006291X04013531

journal_volume

320

pub_type

杂志文章

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