The TRF1-binding protein TERB1 promotes chromosome movement and telomere rigidity in meiosis

Nat Cell Biol. 2014 Feb;16(2):145-56. doi: 10.1038/ncb2896. Epub 2014 Jan 12.

Abstract

During meiotic prophase, telomere-mediated chromosomal movement along the nuclear envelope is crucial for homologue pairing and synapsis. However, how telomeres are modified to mediate chromosome movement is largely elusive. Here we show that mammalian meiotic telomeres are fundamentally modified by a meiosis-specific Myb-domain protein, TERB1, that localizes at telomeres in mouse germ cells. TERB1 forms a heterocomplex with the canonical telomeric protein TRF1 and binds telomere repeat DNA. Disruption of Terb1 in mice abolishes meiotic chromosomal movement and impairs homologous pairing and synapsis, causing infertility in both sexes. TERB1 promotes telomere association with the nuclear envelope and deposition of the SUN-KASH complex, which recruits cytoplasmic motor complexes. TERB1 also binds and recruits cohesin to telomeres to develop structural rigidity, strikingly reminiscent of centromeres. Our study suggests that TERB1 acts as a central hub for the assembly of a conserved meiotic telomere complex required for chromosome movements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Chromosomes*
  • Female
  • Fertility / genetics
  • Male
  • Meiosis*
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Telomere*
  • Telomeric Repeat Binding Protein 1 / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • TERB1 protein, mouse
  • Telomeric Repeat Binding Protein 1