Histone gene "knock-out" in mouse embryonic stem cells / by Varaporn Thonglairoam.

Bibliography: leaves 113-126.v, 126, [113] leaves, [10] leaves of plates : ill. ; 30 cm.Studies the biological significance of the mouse Listone variant H2A.Z. Describes the isolation and characterisation of H2A.Z genomic clones from different mouse genomic libraries; H2A.Z gene targeting in mouse E14 embryonic stem cells; and an attempt to generatae ES cell lines and mice which lack the functional H2A.Z protein to investigate H2A.Z function in vitro and in vivo.Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1995

Histone variant H2A.Z is required for early mammalian development

Fundamental to the process of mammalian development is the timed and coordinated regulation of gene expression. This requires transcription of a precise subset of the total complement of genes. It is clear that chromatin architecture plays a fundamental role in this process by either facilitating or restricting transcription factor binding [1]. How such specialized chromatin structures are established to regulate gene expression is poorly understood. All eukaryotic organisms contain specialized histone variants with distinctly different amino acid sequences that are even more conserved than the major core histones [2]. On the basis of their highly conserved sequence, histone variants have been assumed critical for the function of mammalian chromatin; however, a requirement for a histone variant has not been shown in mammalian cells. Mice with a deletion of H1° have been generated by gene targeting in ES cells, but these mice show no phenotypic consequences, perhaps due to redundancy of function [3]. Here we show for the first time that a mammalian histone variant, H2A.Z, plays a critical role in early development, and we conclude that this histone variant plays a pivotal role in establishing the chromatin structures required for the complex patterns of gene expression essential for normal mammalian development.http://www.sciencedirect.com/science/journal/0960982