Dynamic distribution of linker histone H1.5 in cellular differentiation

PLoS Genet. 2012;8(8):e1002879. doi: 10.1371/journal.pgen.1002879. Epub 2012 Aug 30.


Linker histones are essential components of chromatin, but the distributions and functions of many during cellular differentiation are not well understood. Here, we show that H1.5 binds to genic and intergenic regions, forming blocks of enrichment, in differentiated human cells from all three embryonic germ layers but not in embryonic stem cells. In differentiated cells, H1.5, but not H1.3, binds preferentially to genes that encode membrane and membrane-related proteins. Strikingly, 37% of H1.5 target genes belong to gene family clusters, groups of homologous genes that are located in proximity to each other on chromosomes. H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment, and chromatin compaction. Depletion of H1.5 results in loss of SIRT1 and H3K9me2, increased chromatin accessibility, deregulation of gene expression, and decreased cell growth. Our data reveal for the first time a specific and novel function for linker histone subtype H1.5 in maintenance of condensed chromatin at defined gene families in differentiated human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics*
  • Chromatin / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells / cytology
  • Fibroblasts
  • Gene Expression Regulation, Developmental
  • Germ Cells* / growth & development
  • Germ Cells* / metabolism
  • Heterochromatin / genetics
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Membrane Proteins / genetics
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism


  • Chromatin
  • DNA-Binding Proteins
  • H1-5 protein, human
  • Heterochromatin
  • Histones
  • Membrane Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM6B protein, human
  • SIRT1 protein, human
  • Sirtuin 1

Grants and funding

This work was funded by a California Institute for Regenerative Medicine (CIRM) grant to SKK. J-YL is supported by a training grant of CIRM in stem cell research at UCLA. WEL holds the Maria Rowena Ross Chair in cell biology and is supported by CIRM (RB3-05207). MP is supported by a UCLA training grant in Genetic Mechanisms. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.