Acetylated Histone H2A.Z is a Key Feature of Enhancers and the Promoters of Both Active and Bivalent Genes in Mouse ESCs
Conference Recording Mar 06, 2013
About the Speaker
Emeritus Professor of Biochemistry at the University of Portsmouth, UK, who has been involved in structure/function relationships of histones since the mid-sixties. Initiator in 1988 of chromatin immuno-precipitation techniques using antibodies to acetylated histones and a continuing advocate of this approach to establishing the epigenetic landscape of cells.
H2A.Z is a histone variant conserved from yeast to humans but how it contributes to gene regulation is unclear. It was reported that this variant is exclusively enriched at inactive polycomb target genes in embryonic stem cells (ESCs) (Creyghton et al., Cell 135, p649, 2008) - implying a role in gene repression - despite report of its presence at the promoters of active chicken genes (Bruce et al., NAR 33, p5633, 2005). To resolve this controversy the genome-wide profile of total H2A.Z is compared with that of its hyper-acetylated form in mouse ESCs using xChIP-Seq. H2A.Z is abundant at promoters of both active and ‘poised’ (bivalent) genes, moreover in a hyper-acetylated form, and is accompanied by tri-methylation of histone H3K4. H2A.Z also occupies functional sites in intergenic regions, in particular enhancers and insulators where it is acetylated in some but not all circumstances. In contrast, constitutive heterochromatin totally lacks H2A.Z. Taken together, this epigenetic landscape shows that it is the acetylated form of H2A.Z that occupies the promoters of both active and ‘poised’ genes in mammalian ESCs and the variant is essential for the function of enhancers (in an acetylated form) and insulators/boundaries (in a non-acetylated form).