Active genes in junk DNA? Characterization of DUX genes embedded within 3.3 kb repeated elements

The human genome contains hundreds or. repeats of the 3.3 kb family in regi ons associated with heterochromatin. We have previously isolated a 3.3 kb-l ike cDNA encoding a double homeodomain protein (DUX1). Demonstration that t he protein was expressed in human rhabdomyosarcoma TE671 cells, and charact erization of a homologous promoter suggested that functional DUX genes migh t be present in 3.3 kb elements. In the present study, we describe two near ly identical 3.3 kb/DUX genes derived from PAC 137F16 (DUX3), and TE671 gen omic DNA (DUX5), both mapping to all the acrocentric chromosomes. Their pro moters harbor a GC and a TATAA box, and the open reading frame of the intro nless structural part encodes two DUX proteins differing by alternative tra nslation initiation. The shorter protein of the DUX5 gene is identical to D UX1. Using a protein truncation lest, we could show that these two proteins are encoded by total RNA, but not by poly (A)(+) RNA, from different human tissues and cell lines. Our results indicate that active genes of unusual structure are present in chromosome regions characterized by large amounts of heterochromatic repetitive DNA. (C) 2001 Elsevier Science B.V. All right s reserved.