The murine Bin1 gene functions early in myogenesis and defines a new region of synteny between mouse chromosome 18 and human chromosome 2.
We cloned and functionally characterized the murine Bin1 gene as a first step to investigate its physiological roles in differentiation, apoptosis, and tumorigenesis. The exon-intron organization of the >/=55-kb gene is similar to that of the human gene. Consistent with a role for Bin1 in apoptosis, the promoter included a functional consensus motif for activation by NF-kappaB, an important regulator of cell death. A muscle regulatory module defined in the human promoter that includes a consensus recognition site for myoD family proteins was not conserved in the mouse promoter. However, Bin1 is upregulated in embryonic development by E10.5 in myotomes, the progenitors of skeletal muscle, supporting a role in myogenesis and suggesting that the mouse and human genes may be controlled somewhat differently during development. In C2C12 myoblasts antisense Bin1 prevents induction of the cell cycle kinase inhibitor p21WAF1, suggesting that it acts at an early time during the muscle differentiation program. Interspecific mouse backcross mapping located the Bin1 locus between Mep1b and Apc on chromosome 18. Since the human gene was mapped previously to chromosome 2q14, the location of Bin1 defines a previously unrecognized region of synteny between human chromosome 2 and mouse chromosome 18.
Mao
N C
NC
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania, 19104, USA.
Steingrimsson
E
E
DuHadaway
J
J
Wasserman
W
W
Ruiz
J C
JC
Copeland
N G
NG
Jenkins
N A
NA
Prendergast
G C
GC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000254:growth & development*; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D020161:Physical Chromosome Mapping; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; C109221:Bin1 protein, mouse; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins