A unique H2A histone variant occupies the transcriptional start site of active genes

Nat Struct Mol Biol. 2011 Dec 4;19(1):25-30. doi: 10.1038/nsmb.2161.


Transcriptional activation is controlled by chromatin, which needs to be unfolded and remodeled to ensure access to the transcription start site (TSS). However, the mechanisms that yield such an 'open' chromatin structure, and how these processes are coordinately regulated during differentiation, are poorly understood. We identify the mouse (Mus musculus) H2A histone variant H2A.Lap1 as a previously undescribed component of the TSS of active genes expressed during specific stages of spermatogenesis. This unique chromatin landscape also includes a second histone variant, H2A.Z. In the later stages of round spermatid development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling the transcriptional activation of previously repressed genes. Mechanistically, we show that H2A.Lap1 imparts unique unfolding properties to chromatin. We therefore propose that H2A.Lap1 coordinately regulates gene expression by directly opening the chromatin structure of the TSS at genes regulated during spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Chromatin / genetics
  • Chromatin / metabolism
  • Crystallography, X-Ray
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genetic Variation
  • Histones / chemistry
  • Histones / genetics*
  • Histones / metabolism*
  • Male
  • Meiosis / genetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • Protein Structure, Secondary
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Spermatids / metabolism
  • Spermatogenesis / genetics
  • Transcription Initiation Site*
  • X Chromosome / genetics
  • Y Chromosome / genetics


  • Chromatin
  • Histones
  • Nucleosomes

Associated data

  • GEO/GSE29781