Histone H3 Lys 4 methylation: caught in a bind?

  1. Robert J. Sims III1 and
  2. Danny Reinberg1,2,3
  1. 1Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA;
  2. 2Howard Hughes Medical Institute, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA

This extract was created in the absence of an abstract.

The N termini of nucleosomal histone polypeptides are both highly accessible and extensively modified by various chemical moieties. Interpreting the language of these altered amino acids has evolved into an important area of research. The enzymes that catalyze histone modifications have intimate connections to gene expression. Once it was proposed that these modifications may, in fact, represent a combinatorial “histone code” with distinct instructions pertinent for gene expression (Strahl and Allis 2000; Turner 2000), a rush to better understand chromatin biology ensued. Histone lysine methylation has received considerable attention, in part due to its apparent stability (Bannister et al. 2002), its correlation with disease (Schneider et al. 2002) and cellular identity (Trojer and Reinberg 2006), and the discovery that chromatin domains representing a specific activation state correlate with distinct methylated lysine residues (Sims et al. 2003).

Lysine methylation can exist in three different states, monomethylated (me1), dimethylated (me2), and trimethylated (me3). Intriguingly, studies have indicated that the extent of lysine methylation may be differentially “read” by effector proteins, lending credence to the concept of a histone code. However, despite considerable efforts, the downstream, functional (mechanistic) outcomes of histone lysine methylation remain poorly understood. Generally, transcriptionally silent regions contain H3K9me3 (trimethyl), H3K27me2/3 (di- and trimethyl), and H4K20me1 (monomethyl), whereas active genes correlate with H3K4me2/3 (di- and trimethyl), H3K36me2/3 (di- and trimethyl), and H3K79me2 (dimethyl) (Sims et al. 2003; Margueron et al. 2005; Martin and Zhang 2005). The first proteins demonstrated to directly and specifically interact with methylated histone lysines were associated with the repressive marks H3K9me2/3 and H3K27me2/3. Consistent with this, the downstream consequence of H3K9me and H3K27me recognition is typically considered transcriptional silencing.

The recruitment of effector molecules to histone tails is a suitable working model to explain our current functional understanding of histone lysine methylation. …

Related Articles

| Table of Contents

Life Science Alliance