PMID- 10433963
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190816
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 236
IP  - 1
DP  - 1999 Aug 5
TI  - Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD
      identifies a putative gene within each 3.3 kb element.
PG  - 25-32
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is linked to the polymorphic D4Z4
      locus on chromosome 4q35. In non-affected individuals, this locus comprises
      10-100 tandem copies of members of the 3.3kb dispersed repeat family. Deletions
      leaving 1-8 such repeats have been associated with FSHD, for which no candidate
      gene has been identified. We have determined the complete nucleotide sequence of 
      a 13.5kb EcoRI genomic fragment comprising the only two 3.3kb elements left in
      the affected D4Z4 locus of a patient with FSHD. Sequence analyses demonstrated
      that the two 3.3kb repeats were identical. They contain a putative promoter that 
      was not previously detected, with a TACAA instead of a TATAA box, and a GC box.
      Transient expression of a luciferase reporter gene fused to 191bp of this
      promoter, demonstrated strong activity in transfected human rhabdomyosarcoma
      TE671 cells that was affected by mutations in the TACAA or GC box. In addition,
      these 3.3kb repeats include an open reading frame (ORF) starting 149bp downstream
      from the TACAA box and encoding a 391 residue protein with two homeodomains
      (DUX4). In-vitro transcription/translation of the ORF in a rabbit reticulocyte
      lysate yielded two (35)S Cys/ (35)S Met labeled products with apparent molecular 
      weights of 38 and 75kDa on SDS-PAGE, corresponding to the DUX4 monomer and dimer,
      respectively. In conclusion, we propose that each of the 3.3kb elements in the
      partially deleted D4Z4 locus could include a DUX4 gene encoding a double
      homeodomain protein.
FAU - Gabriels, J
AU  - Gabriels J
AD  - Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
FAU - Beckers, M C
AU  - Beckers MC
FAU - Ding, H
AU  - Ding H
FAU - De Vriese, A
AU  - De Vriese A
FAU - Plaisance, S
AU  - Plaisance S
FAU - van der Maarel, S M
AU  - van der Maarel SM
FAU - Padberg, G W
AU  - Padberg GW
FAU - Frants, R R
AU  - Frants RR
FAU - Hewitt, J E
AU  - Hewitt JE
FAU - Collen, D
AU  - Collen D
FAU - Belayew, A
AU  - Belayew A
LA  - eng
SI  - GENBANK/AF117653
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (DUX1 protein, human)
RN  - 0 (DUX4L1 protein, human)
RN  - 0 (Homeodomain Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 4
MH  - Conserved Sequence
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Genes, Reporter
MH  - Homeodomain Proteins/genetics
MH  - Humans
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Muscular Dystrophies/*genetics
MH  - Mutagenesis
MH  - Open Reading Frames
MH  - Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - Rabbits
MH  - Reticulocytes/metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/08/06 00:00
MHDA- 1999/08/06 00:01
CRDT- 1999/08/06 00:00
PHST- 1999/08/06 00:00 [pubmed]
PHST- 1999/08/06 00:01 [medline]
PHST- 1999/08/06 00:00 [entrez]
AID - S0378-1119(99)00267-X [pii]
AID - 10.1016/s0378-1119(99)00267-x [doi]
PST - ppublish
SO  - Gene. 1999 Aug 5;236(1):25-32. doi: 10.1016/s0378-1119(99)00267-x.