Identification and characterization of reproductive KRAB-ZF genes in mice

Gene. 2015 Jul 1;565(1):45-55. doi: 10.1016/j.gene.2015.03.059. Epub 2015 Mar 28.

Abstract

The mammalian genome contains numerous genes encoding transcription factors that contain Krüppel-associated box (KRAB) and C2H2-type zinc finger (ZF) motifs (KRAB-ZF). In the present study, we identified KRAB-ZF genes expressed in the mouse testis or ovary, and selected three genes that exhibit gonad-specific or gonad-predominant expression. In vitro analyses showed that these gonadal KRAB-ZF proteins are localized in cell nuclei and are able to repress transcriptional activity. We further analyzed one of the gonad-specific reproductive genes, Zfp819, and found that it is expressed exclusively in spermatogenic cells. Overexpression of Zfp819 suppressed cell proliferation and induced apoptosis. Microarray analysis of Zfp819-overexpressing cells allowed us to identify numerous, potential target genes. A number of the down-regulated genes were found to show gene expression levels inversely correlated with Zfp819 during spermatogenesis. Some of the down-regulated genes were previously reported to play significant roles in spermatogenesis and apoptosis. Collectively, our study provides the first comprehensive information regarding the expression of reproductive KRAB-ZF genes in mice and reveals potential functions of Zfp819.

Keywords: Apoptosis; KRAB; Microarray; Spermatogenesis; Testis; Zinc finger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • DNA-Binding Proteins
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gonads / cytology
  • Gonads / metabolism*
  • HEK293 Cells
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Mice
  • NIH 3T3 Cells
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Zinc Fingers

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • Repressor Proteins
  • Zfp819 protein, mouse