A conserved nuclear element with a role in mammalian gene regulation

Mammalian genomes contain numerous fragments of DNA that are derived from i nactivated transposable elements. The accumulation and persistence of these elements is generally attributed to transposase activity rather than throu gh possession or acquisition of a function of value to the host genome. Her e we describe such a repetitive element, named ALF (for annexin VI LINE-2 f ragment), comprising 130 bp of DNA derived from a LINE-2 sequence, which fu nctions as a potent T-cell-specific silencer. The expansion of the DNA data base arising as a result of the human genome sequencing project enabled us to identify ALF in, or close to, several well characterized genes including those for annexin VI, interleukin-4 and protein kinase C-beta. A systemati c analysis of the entire LINE-2 sequence revealed that ALF, and not other r egions of the LINE-2 sequence, was especially highly represented in the hum an genome. Acquisition of a function by this repetitive element may explain its abundance. These data show that a conserved fragment of an intersperse d nuclear element has the potential to modulate gene expression, a discover y that has broad implications for the way in which we view so-called 'junk' DNA and our understanding of eukaryotic gene regulation.