Tài liệu Báo cáo khoa học: Post-translational modifications of the linker histone variants and their

REVIEW ARTICLE

Post-translational modifications of the linker histone

variants and their association with cell mechanisms

Christopher Wood1

, Ambrosius Snijders2

, James Williamson2

, Colin Reynolds1

, John Baldwin3

and Mark Dickman2

1 School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, UK

2 Department of Chemical and Process Engineering, University of Sheffield, UK

3 STFC Daresbury Laboratory, Warrington, UK

Introduction – epigenetic mechanisms

and involvement with disease

Epigenetics is the study of heritable changes in gene

expression that occur without changes in DNA

sequence and, as well as being of fundamental impor￾tance in embryonic development, transcription, chro￾matin structure, X-chromosome inactivation, and

genomic imprinting, it is also now recognized as having

a fundamental role in disease [1]. RNA silencing, DNA

methylation and post-translational modifications

(PTMs) of the core and linker histones are the mechan￾isms that collectively define epigenetics, the latter of

which involve the addition of small chemical groups.

The PTMs that are created by this mechanism include,

but are not limited to, acetylation (lysine), phosphoryla￾tion (serine, threonine), methylation (lysine, arginine),

sumoylation (lysine), and ubiquitination (lysine). Other

epigenetic mechanisms may emerge in the future.

Small RNAs

MicroRNAs (miRNAs) are RNA molecules that are

about 22 nucleotides long and encoded into the

Homo sapiens (hereafter ‘human’) genome [2]. They

Keywords

abundance; acid extraction; cancer; cell

cycle; disease; linker histone; MS;

post-translational modification; PTM;

PTM function

Correspondence

C. M. Wood, School of Pharmacy and

Biomolecular Sciences, Liverpool John

Moores University, Liverpool, UK

Fax: +44 0 51 298 2624

Tel: +44 0 51 231 2565

E-mail: [email protected]

(Received 10 December 2008, revised 23

March 2009, accepted 30 April 2009)

doi:10.1111/j.1742-4658.2009.07079.x

In recent years, a considerable amount of research has been focused on estab￾lishing the epigenetic mechanisms associated with DNA and the core

histones. This effort is driven by the fact that epigenetics is intimately

involved with genomics in a whole range of molecular processes. However,

there is now a consensus that the epigenetics of the linker histones are just as

important. The result of that consensus is that the post-translational modifi￾cations (PTMs) for most of the linker histone variants in human and mouse

have now been established by a number of experimental techniques, foremost

of which is mass spectrometry (MS). MS was also used by our group to

establish the PTMs of the linker histone variants in chicken erythrocytes.

Although it is now known which types of PTM occur at particular locations

on the linker histone variants, there is still a large gap in the knowledge of

how this data relates to function. The focus of this review is an analysis of

the PTM data for the linker histones from several species, but with an empha￾sis on human, mouse, and chicken. Our analysis reveals that certain PTMs

can be clearly correlated with specific functions of the linker histones in par￾ticular cell types, and that unique PTM patterns exist for different cell types.

Abbreviations

CDK, cyclin-dependent kinase; DNMT, DNA methyltransferase; HDAC, histone deacetylase; miRNA, microRNA; MS, mass spectrometry;

PTM, post-translational modification.

FEBS Journal 276 (2009) 3685–3697 ª 2009 The Authors Journal compilation ª 2009 FEBS 3685