The composition and organization of Drosophila heterochromatin are heterogeneous and dynamic

If the DNA in a single human cell is stretched from end to end it is about two meters long, yet it all fits into a space that is just six thousandths of a millimeter across. This feat is possible because protein complexes package the cell’s DNA into a form called chromatin to make it more compact. One type of chromatin – called “heterochromatin” – is needed to ensure that the DNA is positioned properly inside the cell’s nucleus and segregated correctly when the cell divides. Heterochromatin contains many repeated DNA sequences that are repressed or ‘silenced’, as well as some active genes. Though heterochromatin accounts for about 25% of the human genome, little is known about the basic molecular processes that occur in this type of chromatin. This is in part because it is not clear which proteins are present in heterochromatin or how these proteins contribute to its structure and roles within the cell. Swenson, Colmenares et al. have now combined two different approaches to search for proteins that are present in heterochromatin and genes that are needed to regulate heterochromatin’s structure. These searches were conducted using fruit fly cells grown in the laboratory, and identified 118 candidate proteins and 374 candidate genes. Next, Swenson, Colmenares et al. looked more closely at 89 of the proteins and confirmed that 30 did indeed localize to heterochromatin. Unexpectedly, more detailed imaging studies showed that these proteins were often localized to restricted regions within heterochromatin (referred to as subdomains). This closer look also revealed that many of the subdomains are dynamic, because the proteins change where they are localized as the cells grow and divide. Finally, many of the candidate proteins were shown to alter the ability of heterochromatin to silence genes. These findings identify a host of new proteins and genes that bind and regulate heterochromatin. More importantly, Swenson, Colmenares et al. reveal that heterochromatin is structurally complex and contains many dynamic, smaller subdomains. The next critical challenges are to find the molecular mechanisms responsible for this unusual organization and to explore the roles of individual heterochromatin proteins or subdomains.