New insights into the mechanisms of nuclear segmentation in human neutrophils

During human neutrophil differentiation, large portions of the genome conde nse and associate with the nuclear envelope to form filament-like structure s. As a result, the nucleus of the mature neutrophil typically consists of a linear array of three or four lobes joined by thin, DNA-containing filame nts. Despite the medical significance of neutrophil nuclear morphology, lit tle is known about the events regulating neutrophil nuclear differentiation and its pathological states. This work presents a new model of the mechani sms governing nuclear filament formation in human neutrophils. This model i s based on recent chromosome mapping studies in human neutrophils and on st udies of genetic and pathological conditions affecting neutrophil nuclear s hape. According to this model, filament assembly is initiated by factors th at interact with specific regions of the genome in a hierarchical and dose- dependent manner. In this regard, the strategies governing the molecular in teractions responsible for filament formation appear to resemble those invo lved in transcriptional silencing, a phenomenon that also affects the prope rties of extended chromosomal regions. According to the silencing paradigm, bound filament control Factors must recruit additional Filament Foehn fact ors which spread along adjacent DNA to mediate filament formation. A better understanding of the factors that shape the neutrophil nucleus may lead to new clinical tools for the diagnosis and manipulation of abnormal neutroph il differentiation, J. Cell. Biochem. 73:1-10, 1999. (C) 1999 Wiley-Liss, I nc.