Chromatin zigzags

Gene-poor chromosomal regions are more often found in the nuclear periphery, and gene-rich regions are more often found in the nuclear interior. But Shopland et al. (page 27) are the first to analyze how multiple gene-poor and gene-rich regions are organized relative to each other. They find that gene-rich regions often cluster together while pushing interspersing genic deserts to the nuclear periphery, even in the absence of active transcription.

Shopland et al. studied a 4.3-Mb region of mouse chromosome 14 that has four gene-rich regions interspersed with four gene deserts. FISH probes that distinguished the genic and nongenic regions showed that the chromosome bent into three classifiable patterns: a striped pattern that resembled the linear sequence order; a zigzag pattern with the four coding regions next to one another and the gene deserts displaced to one side; and a clustered “hub” of gene-rich segments with peripherally arranged deserts. Combinations of these three patterns were also evident. The deserts often lined up at the edge of the nucleus, where they might contact the lamin meshwork.

The chromosomal arrangements did not appear to depend on transcription at a common site, nor did the gene-rich regions associate with aggregates of RNA splicing factors referred to as speckles. Moreover, the patterns persisted when transcription was blocked by drugs.

Given the limited influence that transcription appeared to have on the genome organization, it remains unclear how or why the chromosome bends into these configurations. The researchers speculate that the gene-rich regions share some regulatory proteins, as might the deserts, and thus are drawn together by cross-talk. There are genes in the region that act in the same developmental pathways, which might support this idea, but while coexpressed they have not been shown to be coregulated. Whether such associations are the result of passive chromatin wiggling or an active pulling process remains to be seen.