Sequence of 10q24 locus surrounding the HOX11 oncogene reveals a new gene HUG1 expressed in a T-ALL cell line.
HOX11 is a gene encoding a homeobox protein which is found to be deregulated in T-cell acute lymphoblastic leukaemia (T-ALL). As a basis for studying the mechanism of deregulation of HOX11 expression in leukaemia, the locus containing the HOX11 proto-oncogene at 10q24 was cloned from a genomic P1 Artificial Chromosome (PAC) library. The PAC clone with an insert size of 120kb was isolated and mapped by restriction analysis. A series of contiguous subclones were then obtained which span 20kb surrounding the HOX11 gene. These subclones were used to sequence across the entire 20kb region to the 3' boundary of the PAC insert. This work provides for the first time the full intron and 5' non-coding sequences of the HOX11 gene which will aid the identification of novel transcriptional control elements which may be involved in silencing HOX11 expression in normal cells. The sequence information was also used to search for novel large open reading frames (ORFs). One such ORF (1.1kb) would encode a protein of at least 39kDa. This basic protein (pI, 12.5) would be very proline rich and could potentially encode a novel transcription factor. In order to establish if this ORF corresponds to a bona fide transcribed gene, RT-PCR analysis was performed. The mRNA for this protein is expressed in the T-ALL cell line Jurkat and has been designated HUG1, for HOX11 Upstream Gene.
TVW Telethon Institute for Child Health Research,1 PO Box 855, West Perth, Western Australia 6872, Australia.
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Watt
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Ranford
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Kees
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D017931:DNA Primers; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D016366:Open Reading Frames; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins
D017931:DNA Primers; D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C071250:TLX1 protein, human