2. Academic Validation
  3. ZZEF1 is a Histone Reader and Transcriptional Coregulator of Krüppel-Like Factors

ZZEF1 is a Histone Reader and Transcriptional Coregulator of Krüppel-Like Factors

  • J Mol Biol. 2021 Jan 22;433(2):166722. doi: 10.1016/j.jmb.2020.11.021.
Yucong Yu 1,  Adam Tencer 2,  Hongwen Xuan 1,  Tatiana G Kutateladze 3,  Xiaobing Shi 4
Affiliations

Affiliations

  • 1 Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
  • 2 Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • 3 Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: [email protected].
  • 4 Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address: [email protected].
PMID: 33227311 DOI: 10.1016/j.jmb.2020.11.021
Abstract

The ZZ-type zinc finger and EF-hand domain protein 1 (ZZEF1) is a multidomain-containing protein. Mutations of ZZEF1 has been implicated in several kinds of human diseases such as diabetes and cancers. However, the function of the ZZEF protein remains largely unknown. Here we show that ZZEF1 functions as a histone H3 reader. The second ZZ domain of ZZEF1 (ZZEF1ZZ2) binds to the N-terminus of histone H3 and is capable of accommodating common epigenetic marks on the H3 tail. The N-terminal Amino acids, especially Ala1, of H3 and an acidic cavity of ZZEF1ZZ2 are critical for the ZZ-H3 interaction. RNA-seq analysis in human lung Cancer cell line H1299 reveals that downregulated genes upon ZZEF1 depletion are specifically enriched in genes regulated by Krüppel-like factors. Indeed, ZZEF1 physically interacts with KLF9 and KLF6, and regulates a common set of target genes of these transcription factors. Together, our findings suggest a model in which ZZEF1 binds to histone H3 tail and promotes KLF9/6-mediated gene regulation.

Keywords

H3; KLF9; Krüppel-like factors; ZZ domain; ZZEF1.

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