The Lasker Awards

In addition to acetylation, eight types of structurally and functionally different short-chain acylations have recently been identified as important histone Lys modifications: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. These modifications are regulated by enzymatic and metabolic mechanisms and have physiological functions, which include signal-dependent gene activation and metabolic stress.

Over the past few decades, epigenetics has evolved from a collection of curious biological phenomena to a functionally dissected research field. In this article, the authors provide a personal perspective on the advances of research into epigenetics — from its historical origins to its modern era — with a focus on molecular breakthroughs.

One of four papers establishing certain PHD domains as effectors of trimethylated histone H3K4, a chromatin mark generally associated with active transcription. This paper shows that the interaction of H3K4me3 with the PHD finger of an ATP-dependent chromatin remodelling complex is involved in control of Hox gene expression during Xenopus development.

An early cellular response to the occurrence of DNA double-strand breaks in mammals is the phosphorylation of the specialized histone variant H2A.X at Ser 139. The chromatin remodelling factor WSTF is found to phosphorylate H2A.X at another site, Tyr 142. Tyrosine phosphorylation has not been observed previously on histones.

Histone post-translational modifications have crucial roles in genome management, in part by recruiting specific factors that alter the structural properties of chromatin. These so-called effector complexes often comprise multiple histone-binding modules that may act in concert to regulate chromatin structure and DNA-related activities.

A chromosomal translocation found in certain acute myeloid leukaemia (AML) patients results in fusion of the plant homeodomain (PHD) finger of a chromatin-binding protein to a common fusion partner, nucleoporin-98 (NUP98). By binding chromatin, the NUP98–PHD fusion protein—found to be a potent oncoprotein that induces AML—apparently locks developmentally important genes into an active state.

Increasing evidence suggests crucial functions for histone variants in diverse biological processes. This Review examines the roles of histone variants in mammalian germ cell and embryonic development, as well as the consequences of their aberrant regulation in human disease.

Finley et al. show that Brd4 is dispensable for self-renewal and pluripotency in murine embryonic stem cells (ESCs). In metastable ESCs, Brd4 independence can be achieved by increasing the expression of the pluripotency transcription factors Oct4, Sox2 and Nanog as long as Tet1/2 are present.

The recent mapping of histone modifications across theSaccharomyces cerevisiaegenome has allowed the analysis of how combinations of modified and unmodified chromatin states relate to each other and particularly to chromosomal landmarks, such as heterochromatin, centromeres, promoters and coding regions.

The X-ray crystal structure and biochemical analysis of a triple helix formed between the expression and nuclear retention element (ENE) and the 3′ poly(A) tail of the human long noncoding RNA MALAT-1 reveals the basis of its stability and how it confers resistance to degradation.