Biomedical subjects

D Wade Abbott

Publications and source records attributed to D Wade Abbott.

5 recordsLinked to original sources

PubMed2005

Beyond the Xi: macroH2A chromatin distribution and post-translational modification in an avian system.

MacroH2A (mH2A) is a histone variant that is enriched in the inactivated X-chromosomes of mammalian females. To characterize the role of this protein in other nuclear processes we isolated chromatin particles from chicken liver, a vertebrate system that does not undergo X-inactivation. Chromatin digestion and fractionation studies determined that mH2A is evenly distributed at several levels of chromatin structure and stabilizes the nucleosome core particle in solution. However, at the level of the chromatosome, selective salt precipitation showed the existence of a mutually exclusive relationship between mH2A and H1, which may reveal functional redundancy between these proteins. Two-dimensional gel electrophoresis demonstrated the presence of one major population of mH2A containing nucleosomes, which may become ADP-ribosylated. This report provides new clues into how mH2A distribution and a previously unidentified post-translational modification may help regulate the repression of autosomal chromatin.

Animals↗

PubMed2004

Histone variant H2ABbd confers lower stability to the nucleosome.

The histone H2ABbd is a novel histone variant of H2A with a totally unknown function. We have investigated the behaviour of the H2ABbd nucleosomes. Nucleosomes were reconstituted with recombinant histone H2ABbd and changes in their conformations at different salt concentrations were studied by analytical centrifugation. The data are in agreement with H2ABbd being less tightly bound compared with conventional H2A in the nucleosome. In addition, stable cell lines expressing either green fluorescent protein (GFP)-H2A or GFP-H2ABbd were established and the mobility of both fusions was measured by fluorescence recovery after photobleaching. We show that GFP-H2ABbd exchanges much more rapidly than GFP-H2A within the nucleosome. The reported data are compatible with a lower stability of the variant H2ABbd nucleosome compared with the conventional H2A particle.

Animals↗

PubMed2004

Structural characterization of macroH2A containing chromatin.

MacroH2A (mH2A) is one of the most recently identified members of the heteromorphous histone variant family. It is unique among the members of this group because it contains an unusually large non-histone C-terminal end, from where its name derives, and appears to be restricted to subphylum vertebrata. Although a concerted effort has been carried out in order to characterize the physiological relevance of mH2A, little is known in comparison about the structural importance of the molecule. Elucidating the biophysical and conformational proprieties of mH2A in chromatin may provide clues into the links between this histone variant and its unique function(s). In this paper, we look first at the heterogeneous tissue-specific distribution of this protein in different vertebrate classes. This is followed by a structural comparison between mH2A and H2A protein and by the characterization of the nucleosome core particles with which these histone subtypes are associated. We find that the highly alpha-helical C-terminus of mH2A confers an asymmetric conformation to nucleosomes and that this variant is tightly bound to chromatin fragments in a way that does not depend on the overall extent of acetylation of the other core histones.

Acetylation↗

PubMed2003

A haploid affair: core histone transitions during spermatogenesis.

The process of meiosis reduces a diploid cell to four haploid gametes and is accompanied by extensive recombination. Thus, the dynamics of chromatin during meiosis are significantly different than in mitotic cells. As spermatogenesis progresses, there is a widespread reorganization of the haploid genome followed by extensive DNA compaction. It has become increasingly clear that the dynamic composition of chromatin plays a critical role in the activities of enzymes and processes that act upon it. Therefore, an analysis of the role of histone variants and modifications in these processes may shed light upon the mechanisms involved and the control of chromatin structure in general. Histone variants such as histone H3.3, H2AX, and macroH2A appear to play key roles in the various stages of spermiogenesis, in addition to the specifically modulated acetylation of histone H4 (acH4), ubiquitination of histones H2A and H2B (uH2A, uH2B), and phosphorylation of histone H3 (H3p). This review will examine recent discoveries concerning the role of histone modifications and variants during meiosis and spermatogenesis.

Acetylation↗

PubMed2002

The many tales of a tail: carboxyl-terminal tail heterogeneity specializes histone H2A variants for defined chromatin function.

For many years, histones were considered to be passive structural components of eukaryotic chromatin. Experimental evidence that has accumulated during the past few years indicates that in addition to their structural role, histones play a very important functional role and that they can operate as epigenetic markers. This notion has rekindled the interest in histone variants and their participation in the processes of chromatin activation and inactivation. Recent papers have focused their attention on histone H2A variants. The variants of this overlooked histone participate in many biological processes ranging from transcriptional activation to DNA repair, meiosis, and apoptosis. A nucleosome containing at least one of these variants has been crystallized and biophysically characterized in solution. From all these results, a new concept has started to emerge, which supports the notion that the functional roles of H2A variants are exerted through alterations in chromatin stability and folding that result from the structural variation at the carboxyl-terminal end of this histone.

Amino Acid Sequence↗