Histone variant H2A.Z is required for early mammalian development

Fundamental to the process of mammalian development is the timed and coordi nated regulation of gene expression. This requires transcription of a preci se subset of the total complement of genes. It is clear that chromatin arch itecture plays a fundamental role in this process by either facilitating or restricting transcription factor binding [1]. How such specialized chromat in structures are established to regulate gene expression is poorly underst ood. All eukaryotic organisms contain specialized histone variants with dis tinctly different amino acid sequences that are even more conserved than th e: 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 degrees have been generated by gene targeting in ES cells, but these mice show no phenotypic consequen ces, 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 earl y development, and we conclude that this histone variant plays a pivotal ro le in establishing the chromatin structures required for the complex patter ns of gene expression essential for normal mammalian development.