Faculty Collaboration Database

Dynamic distribution of linker histone H1.5 in cellular differentiation. PLoS Genet 2012;8(8):e1002879

Date

09/08/2012

Pubmed ID

22956909

Pubmed Central ID

PMC3431313

DOI

10.1371/journal.pgen.1002879

Scopus ID

2-s2.0-84866170632 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

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.

Author List

Li JY, Patterson M, Mikkola HK, Lowry WE, Kurdistani SK

Author

Michaela Patterson PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Differentiation
Chromatin
DNA-Binding Proteins
Embryonic Stem Cells
Fibroblasts
Gene Expression Regulation, Developmental
Germ Cells
Heterochromatin
Histones
Humans
Jumonji Domain-Containing Histone Demethylases
Membrane Proteins
Sirtuin 1