Vertebrate GAF/ThPOK: emerging functions in chromatin architecture and transcriptional regulation

Cell Mol Life Sci. 2018 Feb;75(4):623-633. doi: 10.1007/s00018-017-2633-7. Epub 2017 Aug 30.

Abstract

GAGA factor of Drosophila melanogaster (DmGAF) is a multifaceted transcription factor with diverse roles in chromatin regulation. Recently, ThPOK/c-Krox was identified as its vertebrate homologue (vGAF), which has a basic domain structure similar to DmGAF and is decorated with a number of post-translationally modified residues. In vertebrate genomes, vGAF associates with purine-rich GAGA sequences and performs diverse chromatin-mediated functions, viz., gene activation, repression and enhancer blocking. Expansion of regulatory chromatin proteins with the acquisition of PTMs appears to be the general trend that facilitated the evolution of complexity in vertebrates. Here, we compare the structural and functional features of vGAF with those of DmGAF and also assess the possible functional redundancy among paralogues of vGAF. We also discuss the underlying mechanisms which aid in the diverse and context-dependent functions of this protein.

Keywords: Chromatin regulation; GAGA factor; ThPOK; ZBTB; c-Krox.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Gene Expression Regulation*
  • Humans
  • Regulatory Sequences, Nucleic Acid
  • Sequence Homology
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Vertebrates / genetics

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Transcription Factors
  • Trl protein, Drosophila
  • ZBTB7B protein, human