BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription

1994 ◽  
Vol 14 (10) ◽  
pp. 6773-6788
Author(s):  
A J Franklin ◽  
T L Jetton ◽  
K D Shelton ◽  
M A Magnuson

We report the fortuitous isolation of cDNA clones encoding a novel zinc finger DNA-binding protein termed BZP. The protein encoded is 114 kDa and contains eight zinc finger motifs, seven of which are present in two clusters at opposite ends of the molecule. Both finger clusters bound to the 9-bp sequence AAAGGTGCA with apparent Kds of approximately 2.5 nM. Two of the finger motifs within the amino- and carboxy-terminal finger clusters share 63% amino acid identity. BZP inhibited transcription of the herpes simplex virus thymidine kinase promoter when copies of the 9-bp target motif were linked in cis, suggesting that it functions as a transcriptional repressor. BZP mRNA and immunoreactivity were detected in several established cell lines but were most abundant in hamster insulinoma (HIT) cells, the parental source of the cDNAs. In mouse tissues, BZP mRNA and immunoreactivity were identified in cells of the endocrine pancreas, anterior pituitary, and central nervous system. Interestingly, in HIT cells proliferating in culture, BZP immunoreactivity was predominately nuclear in location, whereas it was usually located in the cytoplasm in most neural and neuroendocrine tissues. Serum deprivation of HIT cells caused BZP immunoreactivity to become predominantly cytoplasmic in location and attenuated its inhibitory effect on transcription, thereby suggesting that the both the subcellular location and the function of this protein are modulated by factors in serum.

1994 ◽  
Vol 14 (10) ◽  
pp. 6773-6788 ◽  
Author(s):  
A J Franklin ◽  
T L Jetton ◽  
K D Shelton ◽  
M A Magnuson

We report the fortuitous isolation of cDNA clones encoding a novel zinc finger DNA-binding protein termed BZP. The protein encoded is 114 kDa and contains eight zinc finger motifs, seven of which are present in two clusters at opposite ends of the molecule. Both finger clusters bound to the 9-bp sequence AAAGGTGCA with apparent Kds of approximately 2.5 nM. Two of the finger motifs within the amino- and carboxy-terminal finger clusters share 63% amino acid identity. BZP inhibited transcription of the herpes simplex virus thymidine kinase promoter when copies of the 9-bp target motif were linked in cis, suggesting that it functions as a transcriptional repressor. BZP mRNA and immunoreactivity were detected in several established cell lines but were most abundant in hamster insulinoma (HIT) cells, the parental source of the cDNAs. In mouse tissues, BZP mRNA and immunoreactivity were identified in cells of the endocrine pancreas, anterior pituitary, and central nervous system. Interestingly, in HIT cells proliferating in culture, BZP immunoreactivity was predominately nuclear in location, whereas it was usually located in the cytoplasm in most neural and neuroendocrine tissues. Serum deprivation of HIT cells caused BZP immunoreactivity to become predominantly cytoplasmic in location and attenuated its inhibitory effect on transcription, thereby suggesting that the both the subcellular location and the function of this protein are modulated by factors in serum.


1990 ◽  
Vol 10 (2) ◽  
pp. 681-688
Author(s):  
G Mardon ◽  
S W Luoh ◽  
E M Simpson ◽  
G Gill ◽  
L G Brown ◽  
...  

The Zfy gene is located on the Y chromosome of placental mammals and encodes a zinc finger protein which may serve as the primary sex-determining signal. A related gene, Zfx, is similarly conserved on the X chromosome. Unlike that in most mammals, the mouse genome contains four homologous zinc finger loci: Zfy-1, Zfy-2, Zfx, and Zfa (on an autosome). We report that, in contrast to the mouse Zfy genes, Zfx is widely transcribed in embryos, newborns, and adults, both male and female. Moreover, Zfx transcripts contain long 3' untranslated sequences which are phylogenetically conserved. Zfa is a processed gene derived from Zfx. An analysis of cDNA clones demonstrated that Zfx encodes a 799-amino-acid protein that is 70% identical to the mouse Zfy-1 and Zfy-2 proteins. Zfx, Zfy-1, and Zfy-2 contain highly acidic amino-terminal domains and carboxy-terminal regions containing 13 zinc fingers. When fused to the DNA-binding domain of GAL4, the acidic domains of Zfx and Zfy-2 activated transcription in yeast cells.


1990 ◽  
Vol 10 (2) ◽  
pp. 681-688 ◽  
Author(s):  
G Mardon ◽  
S W Luoh ◽  
E M Simpson ◽  
G Gill ◽  
L G Brown ◽  
...  

The Zfy gene is located on the Y chromosome of placental mammals and encodes a zinc finger protein which may serve as the primary sex-determining signal. A related gene, Zfx, is similarly conserved on the X chromosome. Unlike that in most mammals, the mouse genome contains four homologous zinc finger loci: Zfy-1, Zfy-2, Zfx, and Zfa (on an autosome). We report that, in contrast to the mouse Zfy genes, Zfx is widely transcribed in embryos, newborns, and adults, both male and female. Moreover, Zfx transcripts contain long 3' untranslated sequences which are phylogenetically conserved. Zfa is a processed gene derived from Zfx. An analysis of cDNA clones demonstrated that Zfx encodes a 799-amino-acid protein that is 70% identical to the mouse Zfy-1 and Zfy-2 proteins. Zfx, Zfy-1, and Zfy-2 contain highly acidic amino-terminal domains and carboxy-terminal regions containing 13 zinc fingers. When fused to the DNA-binding domain of GAL4, the acidic domains of Zfx and Zfy-2 activated transcription in yeast cells.


1990 ◽  
Vol 10 (8) ◽  
pp. 4401-4405 ◽  
Author(s):  
N Kato ◽  
K Shimotohno ◽  
D VanLeeuwen ◽  
M Cohen

RNA transcripts of the HERV-R (ERV3) human provirus that are abundant in placenta but absent in choriocarcinoma contain nonproviral genomic sequences at their 3' ends. We report here the isolation of cDNA clones of these genomic sequences. The transcripts encode a Krüppel-related zinc finger protein consisting of a unique leader region and more than 12 28-amino-acid finger motifs.


1996 ◽  
Vol 42 (9) ◽  
pp. 950-959 ◽  
Author(s):  
Robert A. Shroff ◽  
Robin A. Lockington ◽  
Joan M. Kelly

The molecular nature of a number of creA mutant alleles has been determined. Three alleles analysed are missense mutations in the DNA binding domain and predicted to reduce but not abolish binding. Of the other four alleles, two result from frameshifts: one has a nonsense mutation and the other has an inversion. All four alleles result in truncations of the protein after the zinc finger domain, such that the protein no longer contains at least the carboxy terminal 145 amino acids, so identifying a region required for repression. Transcriptional analysis of creA indicates that the transcript is autoregulated and analysis using 5′ rapid amplification of cDNA ends indicates that transcriptional start points exist in clusters over a region of 200 bp located up to 595 bp 5′ of the translational start point. The two major clusters have potential CREA-binding sites (SYGGRG) at appropriate positions to allow autoregulation. Autoregulation leads to the creA transcript being most abundant in carbon catabolite nonrepressing conditions, and this, together with the phenotypes of the mutant alleles, has led to the suggestion that CREA has effects under conditions generally not considered as carbon catabolite repressing, as well as in carbon catabolite repressing conditions.Key words: carbon catabolite repression, MIG1, CREA, zinc finger protein, transcriptional repressor.


2018 ◽  
Vol 115 (16) ◽  
pp. E3808-E3816 ◽  
Author(s):  
Shady Younis ◽  
Wael Kamel ◽  
Tina Falkeborn ◽  
Hao Wang ◽  
Di Yu ◽  
...  

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A–cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.


Development ◽  
1998 ◽  
Vol 125 (15) ◽  
pp. 2867-2882 ◽  
Author(s):  
J.S. Kuo ◽  
M. Patel ◽  
J. Gamse ◽  
C. Merzdorf ◽  
X. Liu ◽  
...  

In order to study the mechanism of neural patterning in Xenopus, we used subtractive cloning to isolate genes activated early during this process. One gene isolated was opl, (odd-paired-like) that resembles the Drosophila pair-rule gene odd-paired and encodes a zinc finger protein that is a member of the Zic gene family. At the onset of gastrulation, opl is expressed throughout the presumptive neural plate, indicating that neural determination has begun at this stage while, by neurula, opl expression is restricted to the dorsal neural tube and neural crest. opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity. opl both sensitizes animal cap ectoderm to the neural inducer noggin and alters the spectrum of genes induced by noggin, allowing activation of the midbrain marker engrailed. Consistent with the later dorsal neural expression of opl, the activated form of opl is able to induce neural crest and dorsal neural tube markers both in animal caps and whole embryos. In ventral ectoderm, opl induces formation of loose cell aggregates that may indicate neural crest precursor cells. Aggregates do not express an epidermal marker, indicating that opl suppresses ventral fates. Together, these data suggest that opl may mediate neural competence and may be involved in activation of midbrain, dorsal neural and neural crest fates.


1990 ◽  
Vol 10 (8) ◽  
pp. 4401-4405 ◽  
Author(s):  
N Kato ◽  
K Shimotohno ◽  
D VanLeeuwen ◽  
M Cohen

RNA transcripts of the HERV-R (ERV3) human provirus that are abundant in placenta but absent in choriocarcinoma contain nonproviral genomic sequences at their 3' ends. We report here the isolation of cDNA clones of these genomic sequences. The transcripts encode a Krüppel-related zinc finger protein consisting of a unique leader region and more than 12 28-amino-acid finger motifs.


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