Symmetry applied to nuclear microanatomy: a review of gene function and cell differentiation.
The purpose of this paper is to review current knowledge and understandings of gene control and cell differentiation, based upon an appreciation of a possible role that nuclear microanatomy and considerations of steric symmetry might play. Metaphase sister chromatids have identical base codes but show a mirror image symmetry of higher order coiling. Chromosomes in the interphase nucleus have spatially well defined domains and are anatomically distinct and ordered. Chromosomes are known to have interactions i.e. sex chromosome inactivation, PEV, etc. An hypothesis of gene activation is made based on steric interactions among chromosomes and between chromosomes and activating and repressor proteins. These interactions may be influenced by the handedness of higher order chromatid coiling, since homologues show mirror-image symmetrical coiling in metaphase, which might be retained to a certain degree in interphase. This may result in a binary switching of genes. All possible combinations of chromatids in the interphase nucleus, would be enabled by a differential segregation of homologous chromatids at mitosis. To conserve patterns of interchromatid interactions, there must be a programmed segregation of chromatids towards one of the two spindle pole attachments. This orientation might be effected by preferential attachment of microtubules to kinetochore attachment sites, by steric hindrance of the kinetochore by condensed chromatin which initially allows only unidirectional tubule attachment, or possibly by a tethering of interacting chromatids which would migrate en masse. An attempt to apply this hypothesis to some illustrative pathological conditions is made.
Bell
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Division of Anatomical Pathology, Department of Laboratoy Medicine and Pathobiology, St. Michael's Hospital, Faculty of Medicine, The University of Toronto, Toronto, Ontario, Canada. dbell@smh.toronto.on.ca
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000502:physiology*; D002842:Chromatids; D002875:Chromosomes; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008938:Mitosis; D008941:Spindle Apparatus; D015533:Transcriptional Activation