In search of the mechanism that shapes the neutrophil's nucleus

Abstract

The organization of the genome within the confines of the nuclear compartment is considered a key contributor to transcription and DNA replication, repair, and recombination. A typical higher eukaryotic cell has a spherical nucleus that is ∼10 µm in diameter. This is not the case for a neutrophil, a short-lived innate immune cell with an unusual multilobular nuclear structure that may serve purposes outside nuclear functions. In this issue of Genes & Development, Zhu and colleagues (pp. 141-153) investigate the neutrophil's genome organization and the mechanisms that contribute to its unique nuclear shape.

Keywords: Lamin B receptor; genome topology; neutrophils; nucleoli; rDNA.

Figure 1.

Hallmarks of the unique nuclear morphology of a neutrophil. Two subnuclear areas (class A and class B) with mutually exclusive chromosome interactions are depicted for a myeloid progenitor (left) and a differentiated neutrophil (right). The class A area is associated with chromosome regions that are gene-rich and transcriptionally active with open chromatin, whereas class B is rich in DNA repeats and associated with repressed chromatin. Topologically associated chromosome domains (TADs) residing within class A or B areas are color-coded as green or red. Differentiation into a neutrophil is accompanied by displacement of repressed chromosomal regions (class B) that contain centromeres (major satellites), long interspersed nuclear element 1 (LINE-1), and ribosomal DNA (rDNA) repeat elements from the nuclear interior into the nuclear periphery with supercontraction. A change in the abundance of structural proteins such as Lamin B is indicated. The release of neutrophil extracellular traps (NETs) that contain chromatin and antibacterial proteins as part of a process that eliminates invading micro-organisms is also shown.