Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes

Nucleic Acids Res. 2012 Nov;40(21):10950-63. doi: 10.1093/nar/gks839. Epub 2012 Sep 10.

Abstract

Piwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in transposon silencing in the male germline of fetal and newborn mice. Both are also present in adult testes; however, their function here remains a mystery. Here, we confirm that most piRNAs in meiotic spermatocytes originate from clusters in non-repeat intergenic regions of DNA. The regulation of these piRNA clusters, including the processing of the precursor transcripts into individual piRNAs, is accomplished through mostly unknown processes. We present a possible regulatory mechanism for one such cluster, named cluster 1082B, located on chromosome 7 in the mouse genome. The 1082B precursor transcript and its 788 unique piRNAs are repressed by the Alkbh1 dioxygenase and the testis-specific transcription repressor Tzfp. We observe a remarkable >1000-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1- and Tzfp-deficient murine testes. Repression of cluster 1082B is further supported by the identification of a 10-bp Tzfp recognition sequence contained within the precursor transcript. Downregulation of LINE1 and IAP transcripts in the Alkbh1- and Tzfp-deficient mice leads us to propose a potential role for the 1082B-encoded piRNAs in transposon control.

MeSH terms

  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Animals
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / physiology*
  • Down-Regulation
  • Gene Expression Regulation*
  • Genes, Intracisternal A-Particle
  • Long Interspersed Nucleotide Elements
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Pachytene Stage / genetics*
  • RNA Precursors / metabolism
  • RNA, Small Interfering / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Spermatocytes / metabolism*
  • Testis / metabolism

Substances

  • RNA Precursors
  • RNA, Small Interfering
  • Repressor Proteins
  • Rog protein, mouse
  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Alkbh1 protein, mouse
  • DNA-(Apurinic or Apyrimidinic Site) Lyase

Associated data

  • GENBANK/GSE37150