Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family.
The SWI2/SNF2 gene family has been implicated in a wide variety of processes, involving regulation of DNA structure and chromatin configuration, mitotic chromosome segregation, and DNA repair. Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a site in the myosin light chain 1/3 enhancer. The protein has single-stranded DNA-dependent ATPase activity, includes seven helicase motifs, and a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spliced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor lines and in Li-Fraumeni fibroblast cultures, suggesting that it is aberrantly regulated in malignant cells. The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product.
Gong
X
X
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Kaushal
S
S
Ceccarelli
E
E
Bogdanova
N
N
Neville
C
C
Nguyen
T
T
Clark
H
H
Khatib
Z A
ZA
Valentine
M
M
Look
A T
AT
Rosenthal
N
N
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003001:Cloning, Molecular; D004265:DNA Helicases; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology; D018994:Myosin Light Chains / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D018994:Myosin Light Chains; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; D004265:DNA Helicases