Repetitive transgenes in C. elegans accumulate heterochromatic marks and are sequestered at the nuclear envelope in a copy-number- and lamin-dependent manner.

Chromatin is nonrandomly distributed in nuclear space, yet the functional significance of this remains unclear. Here, we make use of transgenes carrying developmentally regulated promoters to study subnuclear gene positioning during the development of Caenorhabditis elegans. We found that small transgenes (copy number ≤50) are randomly distributed in early embryonic nuclei, independent of promoter activity. However, in differentiated tissues, these same transgenes occupied specific subnuclear positions: When promoters are repressed, transgenes are found at the nuclear periphery, whereas active, developmentally regulated promoters are enriched in the nuclear core. The absence of specific transgene positioning in embryonic nuclei does not reflect an absence of proteins that mediate perinuclear sequestration: Embryonic nuclei are able to sequester much larger transgene arrays (copy number 300-500) at the periphery. This size-dependent peripheral positioning of gene arrays in early embryos correlates with the accumulation of heterochromatic marks (H3K9me3 and H3K27me3) on large arrays. Interestingly, depletion of nuclear lamina components caused release of arrays from the nuclear envelope and interfered with their efficient silencing. Our results suggest that developmentally silenced chromatin binds the nuclear lamina in a manner correlated with the deposition of heterochromatic marks. Peripheral sequestration of chromatin may, in turn, support the maintenance of silencing.