Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold.

• 影响指数: 3.322
• 发表时间: Jun 2014 27
• 来源期刊: Biochem Biophys Res Commun
• DOI: 10.1016/j.bbrc.2014.05.018
• PMID: 24835951
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Golla JP,Zhao J,Mann IK,Sayeed SK,Mandal A,Rose RB,Vinson C

关键词: Basic-helix-loop-helix; CG dinucleotide; Carboxylation; DNA binding; E-Box motif; Tcf3|Ascl1 heterodimer

Mesh: 5-Methylcytosine / chemistry metabolism; Amino Acid Sequence; Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors / chemistry genetics metabolism; Circular Dichroism; Cytosine / analogs & derivatives chemistry metabolism; Dinucleoside Phosphates / chemistry metabolism; E-Box Elements; Humans; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Multimerization

Abstract

Three oxidative products of 5-methylcytosine (5mC) occur in mammalian genomes. We evaluated if these cytosine modifications in a CG dinucleotide altered DNA binding of four B-HLH homodimers and three heterodimers to the E-Box motif CGCAG|GTG. We examined 25 DNA probes containing all combinations of cytosine in a CG dinucleotide and none changed binding except for carboxylation of cytosine (5caC) in the strand CGCAG|GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3|Ascl1 heterodimer which increased binding ~10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors.