bZIP Dimers CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun Prefer to Bind to Some Double-Stranded DNA Sequences Containing 5-Formylcytosine and 5-Carboxylcytosine

Biochemistry. 2020 Sep 29;59(38):3529-3540. doi: 10.1021/acs.biochem.0c00475. Epub 2020 Sep 20.

Abstract

In mammalian cells, 5-methylcytosine (5mC) occurs in genomic double-stranded DNA (dsDNA) and is enzymatically oxidized to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxylcytosine (5caC). These cytosine modifications are enriched in regulatory regions of the genome. The effect of these oxidative products on five bZIP dimers (CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun) binding to five types of dsDNA was measured using protein binding microarrays. The five dsDNAs contain either cytosine in both DNA strands or cytosine in one strand and either 5mC, 5hmC, 5fC, or 5caC in the second strand. Some sequences containing the CEBP half-site GCAA are bound more strongly by all five bZIP domains when dsDNA contains 5mC, 5hmC, or 5fC. dsDNA containing 5caC in some TRE (AP-1)-like sequences, e.g., TGACTAA, is better bound by Zta, ATF3|cJun, and cFos|cJun.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • 5-Methylcytosine / chemistry
  • Amino Acid Sequence
  • Animals
  • Basic-Leucine Zipper Transcription Factors / chemistry
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • DNA / chemistry
  • DNA / metabolism*
  • Mice
  • Protein Array Analysis
  • Protein Binding

Substances

  • 5-carboxylcytosine
  • 5-formylcytosine
  • Basic-Leucine Zipper Transcription Factors
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine
  • DNA