Detection of DNA Modifications by Sequence-Specific Transcription Factors

Jie Yang, Xing Zhang, Robert M. Blumenthal, Xiaodong Cheng

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

The establishment, detection, and alteration or elimination of epigenetic DNA modifications are essential to controlling gene expression ranging from bacteria to mammals. The DNA methylations occurring at cytosine and adenine are carried out by SAM-dependent methyltransferases. Successive oxidations of 5-methylcytosine (5mC) by Tet dioxygenases generate 5-hydroxymethyl (5hmC), 5-formyl (5fC), and 5-carboxyl (5caC) derivatives; thus, DNA elements with multiple methylation sites can have a wide range of modification states. In contrast, oxidation of N6-methyladenine by homologs of Escherichia coli AlkB removes the methyl group directly. Both Tet and AlkB enzymes are 2-oxoglutarate- and Fe(II)-dependent dioxygenases. DNA-binding proteins decode the modification status of specific genomic regions. This article centers on two families of sequence-specific transcription factors: bZIP (basic leucine-zipper) proteins, exemplified by the AP-1 and CEBPβ recognition of 5mC; and bHLH (basic helix-loop-helix) proteins, exemplified by MAX and TCF4 recognition of 5caC. We discuss the impact of template strand DNA modification on the activities of DNA and RNA polymerases, and the varied tendencies of modifications to alter base pairing and their interactions with DNA repair enzymes.

Original languageEnglish (US)
Pages (from-to)1661-1673
Number of pages13
JournalJournal of Molecular Biology
Volume432
Issue number6
DOIs
StatePublished - Mar 13 2020

Keywords

  • Basic helix-loop-helix (bHLH) proteins
  • Basic leucine-zipper (bZIP) proteins
  • DNA adenine methylation
  • DNA cytosine methylation
  • Modification-responsive transcription factors

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Detection of DNA Modifications by Sequence-Specific Transcription Factors'. Together they form a unique fingerprint.

Cite this