Sometimes size does matter

10.1083/jcb/1722iti3jcb1722iti3Sometimes size does matter D uring myofi broblast differentiation in vitro, “supermature” focal adhesions (FAs) arise due to increased physical stress, report Goffi n et al. (page 259). Additionally, increased tension induces accumulation of αsmooth muscle actin (α-SMA) in stress fi bers that are anchored at these FAs. In vivo, the extracellular matrix rearranges and increases in rigidity in response to wounding. This change, along with the release of growth factors, induces fi broblasts to take on a contractile phenotype, including expression of α-SMA. The question remains, however, as to what triggers incorporation of α-SMA into stress fi bers in these cells. When differentiated myofi broblasts were cultured on fl exible substrates, FAs remained relatively small. However when the cells were grown on rigid substrates, supermature FAs formed. Once formed, supermature FAs were able to withstand substantially larger physical forces and generated higher intracellular tension than did FAs of a more typical size. This higher tension in turn triggered α-SMA recruitment to stress fi bers, which did not occur in cells with smaller FAs. The team is working to identify the cellular component that senses the increased tension in stress fi bers and recruits α-SMA. In the meantime, they are convinced that tension and size are intimately linked in the formation of supermature FAs and α-SMA stress fi bers. α-smooth muscle actin (blue) joins stress fi bers that are under a lot (left) but not less (right) tension. O n page 177, Brown et al. follow the nuclear positioning of the globin genes during erythroid differentiation and fi nd that they are often close to each other during active transcription. However, such associations do not appear to be a requirement for transcriptional regulation, but rather a consequence of it. The αand β-globin genes are highly transcribed for a brief time during the maturation of red blood cells, with each gene producing about the same amount of mRNA. But the chromosomal contexts for the genes are very different. The human α-globin genes lie in a gene-dense subtelomeric region that is constitutively in an open chromatin conformation. The β-globin genes are in an AT-rich region that is open only during erythroblast development. At the point of maximal transcription, the α-globin genes were frequently decondensed and distinct from their chromosomal territories. By contrast, the β-globin genes remained close to their native chromosome arms, as did the mouse α-globin genes, which lie in a less generich region than their human counterparts. Moreover, the human α-globin alleles associated near one another in approximately half of the transcribing cells examined, as did αand β-globin alleles. β-globin alleles, in contrast, were almost never in close proximity to each other. Finally, the α-globin alleles were more likely to be in contact with large aggregates of splicing factors called speckles. Thus, despite the functional similarities of human and mouse αand β-globin genes, the loci show differing patterns of nuclear localization and interaction. Brown et al. conclude that gene positioning in the nucleus depends on multiple factors, including gene density and chromosomal location. They hypothesize that rapidly transcribed genes—or at least those that are potentially mobile—can be pulled near one another as large aggregates of transcription and processing factors accumulate in their vicinity. Already, they have seen similar associations between other coexpressed genes. α-globin genes (green) can stay near (left) or stray away (right) from their home territories (red).