Chromatin and gene regulation at the onset of embryonic development.
Major transitions in chromosome and chromatin structure occur during development. Recent genetic and biochemical experiments demonstrate that these alterations in genome organization make significant contributions to establishing and maintaining states of differential transcriptional activity. Developmentally regulated changes in histone variants have a causal role in determining patterns of gene activity, directing the repression of specific eukaryotic genes. Chromosomal proteins such as Polycomb stabilize and maintain transcriptionally repressed states. Proteins regulating mitotic chromosome condensation have a role in determining the overall transcriptional activity of a chromosome. In this review, I place the developmental roles of these chromosomal constituents in a structural and functional context. Considerable insight now exists into the molecular mechanisms regulating chromosomal activity during development. Chromosomal architecture is emerging as a key controlling influence in the developmental regulation of gene expression. Recent genetic experiments using Caenorhabditis elegans, Drosophila melanogaster and the mouse have provided clear evidence for the functional differentiation of chromosomal structures during development. Chromosomes are visualized as highly specialized entities, within which the activity of particular domains is largely determined by defined structural proteins. At a more local level, the mechanisms regulating gene transcription during early embryogenesis in Xenopus and the mouse have been found to be dependent on the biochemical composition of individual nucleosomes. Thus, variation in the type and modification of chromosomal and chromatin structural proteins provides a dominant means of controlling the transcriptional activity of individual genes, individual chromosomal domains and of entire chromosomes. The focus of this review is to summarize these recent advances and to discuss their implications for developmental biology.
Wolffe
A P
AP
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-5431, USA.
D000818:Animals; D002843:Chromatin / Q000737:chemistry; D002875:Chromosomes / Q000648:ultrastructure; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D009707:Nucleosomes / Q000648:ultrastructure
D002843:Chromatin; D009707:Nucleosomes