Chromatin Remodeling with Oocyte-specific Linker Histones

The term ‘epigenetics’ defines all meiotically and mitotically heritable changes in gene expression that are not coded in the DNA sequence itself. Epigenetic modification of the genome ensures proper gene activation during development and involves genomic methylation changes, the assembly of histones and histone variants into nucleosomes, and remodeling of other chromatin associated proteins such as linker histones and transcription factors [1]. Additionally, the economic and medical implications of widespread cloning of domestic animals by nuclear transfer have greatly stimulated interest in the basic molecular mechan i sms i nvo l ved i n r ep rog ramming t he developmental fate of nuclei introduced into eggs and oocytes [2]. An understanding of these mechanisms not only wi l l provide insight into the signi f icance of epigenetic events in establishing a developmental program, but also suggests new approaches towards improving the efficiency of nuclear transfer procedures. The fundamental structural unit of chromatin is an assemblage, called the nucleosome, composed of five types of histones (designated H1, H2A, H2B, H3, and H4) and DNA. A nucleosome consists of approximately 1.8 turns of DNA wound around a core particle of histone proteins. The core particle is an octamer of 4 types of histones: two each of the H2A, H2B, H3, and H4 proteins. Approximately 166 base pairs are bound to the nucleosome: 146 base pairs are tightly bound to the core particle and the remaining 20 base pairs are associated with the H1 histone [3]. This nucleosome structure is closely similar in all eukaryotes. Although the f ie ld of chromatin research has focused on modifications to core histones that signal different gene expression states, it is becoming clear that different subtypes of histones are also important. Recently, Lee et al. demonstrate how a linker histone, H1b, can specifically repress the expression of a regulator of skeletal muscle differentiation, the MyoD gene, and thereby restrain the developmental decision to make muscle [4]. They speculate that the complexity of H1 function is attributed, in part, to differential activities of its isoforms.