4.8 Article

AC-motif: a DNA motif containing adenine and cytosine repeat plays a role in gene regulation

期刊

NUCLEIC ACIDS RESEARCH
卷 49, 期 17, 页码 10150-10165

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OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab728

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资金

  1. Samsung Science & Technology Foundation [SSTFBA1301-01]
  2. National Research Foundation of Korea [2020R1A4A1018019, 2021R1A2C3011644, 2021R1A2C3012908]
  3. Korea Basic Science Institute [C140440]
  4. Ministry of Science and ICT
  5. National Research Foundation of Korea [2021R1A2C3011644, 2020R1A4A1018019, 2021R1A2C3012908] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The study identifies a stable secondary structure, termed 'adenine:cytosine-motif (AC-motif)', formed by adenine and cytosine repeats in DNA sequences, which is similar to the i-motif structure. This AC-motif plays a key regulatory role in gene expression in response to magnesium, expanding the repertoire of non-canonical DNA structures with potential regulatory functions in cells.
I-motif or C4 is a four-stranded DNA structure with a protonated cytosine:cytosine base pair (C+:C) found in cytosine-rich sequences. We have found that oligodeoxynucleotides containing adenine and cytosine repeats form a stable secondary structure at a physiological pH with magnesium ion, which is similar to i-motif structure, and have named this structure 'adenine:cytosine-motif (AC-motif)'. AC-motif contains C+:C base pairs intercalated with putative A(+):C base pairs between protonated adenine and cytosine. By investigation of the AC-motif present in the CDKL3 promoter (AC-motif(CDKL3)), one of AC-motifs found in the genome, we confirmed that AC-motif(CDKL3) has a key role in regulating CDKL3 gene expression in response to magnesium. This is further supported by confirming that genome-edited mutant cell lines, lacking the AC-motif formation, lost this regulation effect. Our results verify that adenine-cytosine repeats commonly present in the genome can form a stable non-canonical secondary structure with a non-Watson-Crick base pair and have regulatory roles in cells, which expand non-canonical DNA repertoires.

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