A conserved nuclear element with a role in mammalian gene regulation.
Mammalian genomes contain numerous fragments of DNA that are derived from inactivated transposable 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 (forannexin VILINE-2fragment), 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-beta. A systematic analysis of the entire LINE-2 sequence revealed that ALF, and not other regions of the 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.
Donnelly
S R
SR
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Hawkins
T E
TE
Moss
S E
SE
D000818:Animals; D017317:Annexin A6 / Q000235:genetics*; D001483:Base Sequence; D017124:Conserved Sequence; D004251:DNA Transposable Elements / Q000235:genetics*; D016208:Databases, Factual; D019143:Evolution, Molecular; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D013601:T-Lymphocytes
D017317:Annexin A6; D004251:DNA Transposable Elements; D012333:RNA, Messenger