Nonrandom location and orientation of the inactive X chromosome in human neutrophil nuclei

The nuclei of human neutrophils typically consist of a linear array of thre e or four lobes joined by DNA-containing filaments. Terminal lobes are conn ected to internal lobes via a single filament, while internal lobes have tw o filaments, each to an adjacent lobe. Some lobes also have appendages of v arious shapes and sizes. In particular, up to 17% of neutrophil nuclei of h ealthy women exhibit a drumstick-shaped appendage that contains the inactiv e X chromosome. This report provides a detailed analysis of the relationshi p between nuclear morphology and the location of the X and Y chromosomes in human neutrophils. Fluorescent in situ hybridization analysis revealed tha t the X and the Y chromosomes of male neutrophil nuclei are randomly distri buted among nuclear lobes. Similarly, in female neutrophil nuclei with a dr umstick appendage, the active X chromosome is also randomly distributed amo ng lobes. In contrast, the inactive X chromosome is preferentially located in a terminal lobe in over 90% nuclei with drumsticks. Within the terminal lobe of nuclei with drumsticks, the inactive X chromosome lies distal to th e point of filament attachment in 80% of the nuclei. The inactive X chromos ome also exhibits a specific orientation within the drumstick appendage, wi th over 95% of nuclei having the X centromere located toward the tip of the appendage. Female nuclei without a drumstick appendage also have one of th e X chromosomes (presumably the inactive chromosome) preferentially situate d in a terminal lobe. Nonrandom distribution of the inactive X chromosome i s discussed in the context of a model that considers chromosomes as determi nants of neutrophil nuclear morphology.