A Conserved Nuclear Element with a Role in Mammalian Gene Regulation

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Abstract
Mammalian genomes contain numerous fragments of DNA that are derived from inactivated transposa-ble elements. The accumulation and persistence of these elements is generally attributed to transposase activity rather than through possession or acquisition of a function of value to the host genome. Here we describe such a repetitive element, named ALF (for annexin VI LINE-2 fragment), comprising 130 bp of DNA derived from a LINE-2 sequence, which functions as a potent T-cell-specific silencer. The expansion of the DNA database 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-β. A systematic analysis of the entire LINE-2 sequence revealed that ALF, and not other regions ofthe LINE-2 sequence, was especially highly represented in the human genome. Acquisition of a function by this repetitive element may explain its abundance. These data show that a conserved fragment of an interspersed nuclear element has the potential to modulate gene expression, a discovery that has broad implications for the way in which we view so-called ‘junk’ DNA and our understanding of eukaryotic gene regulation.