Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails

  1. Yi Zhang1,3 and
  2. Danny Reinberg2,4
  1. 1Department of Biochemistry and Biophysics, Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA; 2Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA

This extract was created in the absence of an abstract.

In this review, we discuss recent advances made on histone methylation and its diverse functions in regulating gene expression. Methylation of histone polypeptides might be static and might mark a gene to be or not be transcribed. However, the decision to methylate or not methylate a specific residue in the histone polypeptides is an active process that requires coordination among different covalent modifications occurring at the amino termini of the histone polypeptides, the histone tails. Below, we summarize recent advances on histone methyltransferases, and we discuss histone methylation within the context of other histone tail modifications.

Histone modifications and the histone code hypothesis

In eukaryotic cells, genes are complexed with core histones and other chromosomal proteins in the form of chromatin. The basic repeating unit of chromatin, the nucleosome, includes two copies of each of the four core histones H2A, H2B, H3, and H4 wrapped by 146 bp of DNA. With the aid of additional proteins, including histone H1, the nucleosomes are further packaged into 30-nm fibers with six nucleosomes per turn in a spiral or solenoid arrangement (Kornberg and Lorch 1999;Hayes and Hansen 2001). The 30-nm fiber unfolds to generate a template for transcription, an 11-nm fiber or beads on a string, by a mechanism that is not entirely clear. However, it is thought that unfolding involves post-translational modifications, particularly acetylation, of the core histone amino-terminal tails.

The 11-nm fiber is also repressive to processes requiring access of proteins to DNA. Recent studies have revealed that there are different types of protein complexes capable of altering the chromatin, and these may act in a physiological context to modulate DNA accessibility. One family includes multiprotein complexes that utilize the energy derived from ATP hydrolysis to mobilize or alter the structure of nucleosomes (Kingston and Narlikar 1999; Vignali et al. 2000). The other family includes …

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