Tài liệu Báo cáo khoa học: Mixed lineage leukemia: histone H3 lysine 4 methyltransferases from yeast

MINIREVIEW

Mixed lineage leukemia: histone H3 lysine 4

methyltransferases from yeast to human

Shivani Malik and Sukesh R. Bhaumik

Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL, USA

Introduction

The DNA in eukaryotes is compacted in the form of

chromatin. The fundamental unit of chromatin is the

nucleosome which consists of a core histone particle

with 146 bp of DNA wrapped around it [1,2]. The core

histone particle comprises a tetramer of histones H3 and

H4 and dimers of histones H2A and H2B [2]. Each of

these histones has a structured core globular domain

and an unstructured flexible N-terminal tail protruding

from the core domain. The linker histone H1 associates

with the core domain to form a higher order structure,

thus further compacting the DNA [3,4]. Such compac￾tion of DNA in a higher order chromatin structure

makes it inaccessible for proteins involved in different

DNA-transacting processes such as transcription, repli￾cation, recombination and DNA repair. However, the

chromatin structure has to be dynamic in nature in

order for DNA-transacting processes to occur [5–10],

and such dynamic states are regulated by ATP-depen￾dent chromatin remodelers as well as by ATP-indepen￾dent histone covalent modifications.

There are several ATP-dependent chromatin remo￾delers. These include the switching–defective ⁄sucrose

non-fermenting (SWI⁄ SNF), imitation switch (ISW1),

nucleosome remodeling and histone deacetylation

(Mi-2 ⁄ NuRD), and INO80 complexes [11–25]. These

complexes have a catalytic ATPase subunit with

Keywords

ASH1; ASH2; COMPASS; histone H3

lysine 4; histone methyltransferase; MLL;

Set1; TAC1; TRX; WDR5

Correspondence

S. R. Bhaumik, Department of Biochemistry

and Molecular Biology, Southern Illinois

University School of Medicine, Carbondale,

IL 62901, USA

Fax: +1 618 453 6440

Tel: +1 618 453 6479

E-mail: [email protected]

(Received 16 November 2009, revised

12 January 2010, accepted 22 January

2010)

doi:10.1111/j.1742-4658.2010.07607.x

The fourth lysine of histone H3 is post-translationally modified by a methyl

group via the action of histone methyltransferase, and such a covalent

modification is associated with transcriptionally active and ⁄ or repressed

chromatin states. Thus, histone H3 lysine 4 methylation has a crucial role

in maintaining normal cellular functions. In fact, misregulation of this

covalent modification has been implicated in various types of cancer and

other diseases. Therefore, a large number of studies over recent years have

been directed towards histone H3 lysine 4 methylation and the enzymes

involved in this covalent modification in eukaryotes ranging from yeast to

human. These studies revealed a set of histone H3 lysine 4 methyltransfe￾rases with important cellular functions in different eukaryotes, as discussed

here.

Abbreviations

ASH1, absent, small or homeotic discs 1; ASH2, absent, small or homeotic discs 2; BRM, brahma; CBP, CREB-binding protein; EcR,

ecdysone receptor; HAT, histone acetyl transferase; H3K4, histone H3 lysine 4; HMT, histone methyltransferase; MLL, mixed lineage

leukemia; MOF, male absent on the first; Paf1, RNA polymerase II-associated factor 1; PcG, polycomb group; PHD, plant homeodomain;

TAC1, trithorax acetylation complex 1; TRR, trithorax-related; TRX, trithorax.

FEBS Journal 277 (2010) 1805–1821 ª 2010 The Authors Journal compilation ª 2010 FEBS 1805