H1 histones: current perspectives and challenges

Abstract

H1 and related linker histones are important both for maintenance of higher-order chromatin structure and for the regulation of gene expression. The biology of the linker histones is complex, as they are evolutionarily variable, exist in multiple isoforms and undergo a large variety of posttranslational modifications in their long, unstructured, NH2- and COOH-terminal tails. We review recent progress in understanding the structure, genetics and posttranslational modifications of linker histones, with an emphasis on the dynamic interactions of these proteins with DNA and transcriptional regulators. We also discuss various experimental challenges to the study of H1 and related proteins, including limitations of immunological reagents and practical difficulties in the analysis of posttranslational modifications by mass spectrometry.

Figure 1.

A search of PubMed for primary research articles containing histone H1 or histone H3 in the title or abstract. Data show a steady-state low number (<100) of publications for histone H1, whereas histone H3 displays an increasing trend over time.

Figure 2.

Sequence alignment of histone H1 variants. (A) Amino acid sequence alignment for the histone H1 variants H1.2, H1.3, H1.4 and H1.5. (B) Pairwise scores of sequence homology. The alignment shows a high homology between the human H1 variants.

Figure 3.

An illustration of the MS-identified posttranslational modifications on histone H1.4. Asterisk denotes N-α-acetylation of the N-terminal residue after methionine removal.

Figure 4.

A graphical representation of the tryptic peptide length (A) and a histogram of relative hydrophobicities (B) for histone H1.4, histone H4 and bovine serum albumin.