N160 of Aiolos Determines its DNA-Binding Activity

Anat Rec (Hoboken). 2019 Nov;302(11):2014-2019. doi: 10.1002/ar.24213. Epub 2019 Jul 11.

Abstract

Aiolos is a transcription factor of the Ikaros family. It is expressed in lymphocytes and plays a vital role in the development of lymphatic system. Recently, Aiolos has been found to be ectopically expressed in lung cancer cells and promotes cancer metastasis through repression of p66Shc expression. Blocking DNA-binding activity of Aiolos may benefit cancer patients by preventing further metastasis. However, it is not clear which sequence is essential for its DNA binding. In this study, we found that N160 is a key amino acid to determine the DNA-binding activity of Aiolos. Mutation of N160A resulted in loss of peripheral heterochromatin localization and dissociation with its target gene. Accordingly, Aiolos with N160A could not change the expression of its target genes. Thus, we identified the amino acid (N160) that is essential for Aiolos binding to DNA. Anat Rec, 302:2014-2019, 2019. © 2019 American Association for Anatomy.

Keywords: Aiolos; DNA binding; N160; transcriptional regulation.

MeSH terms

  • A549 Cells
  • Amino Acids / chemistry*
  • Amino Acids / genetics
  • Amino Acids / metabolism
  • DNA / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / metabolism*
  • Mutation*
  • Src Homology 2 Domain-Containing, Transforming Protein 1 / genetics
  • Src Homology 2 Domain-Containing, Transforming Protein 1 / metabolism*

Substances

  • Amino Acids
  • DNA-Binding Proteins
  • IKZF3 protein, human
  • SHC1 protein, human
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Ikaros Transcription Factor
  • DNA