Tuning the reactivity of Sp1 zinc fingers with platinum complexes

2016 ◽  
Vol 45 (21) ◽  
pp. 8712-8716 ◽  
Author(s):  
Zhifeng Du ◽  
Raphael E. F. de Paiva ◽  
Yun Qu ◽  
Nicholas Farrell
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Lewis Acid ◽  
Zinc Fingers ◽  
Platinum Complexes ◽  
Coordination Unit ◽  
Transcription Factor Sp1 ◽  
Dinuclear Platinum

The microenvironment around a zinc finger coordination unit affects the reactivity of apparently similar ZFs with Lewis acid platinum electrophiles. The unique dicysteine-bridged dinuclear platinum unit is the product of the reaction of [PtCl2(en)] and the F3 of the transcription factor Sp1.

scholarly journals Inhibition of red blood cell development by arsenic-induced disruption of GATA-1

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xixi Zhou ◽  
Sebastian Medina ◽  
Alicia M. Bolt ◽  
Haikun Zhang ◽  
Guanghua Wan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Zinc Fingers ◽  
Arsenic Exposure ◽  
In Vivo Studies ◽  
Regulatory Factor ◽  
Zinc Finger Motifs ◽  
First Time

Abstract Anemia is a hematological disorder that adversely affects the health of millions of people worldwide. Although many variables influence the development and exacerbation of anemia, one major contributing factor is the impairment of erythropoiesis. Normal erythropoiesis is highly regulated by the zinc finger transcription factor GATA-1. Disruption of the zinc finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this critical transcription factor and causes dyserythropoietic anemia. Herein, we utilize a combination of in vitro and in vivo studies to provide evidence that arsenic, a widespread environmental toxicant, inhibits erythropoiesis likely through replacing zinc within the zinc fingers of the critical transcription factor GATA-1. We found that arsenic interacts with the N- and C-terminal zinc finger motifs of GATA-1, causing zinc loss and inhibition of DNA and protein binding activities, leading to dyserythropoiesis and an imbalance of hematopoietic differentiation. For the first time, we show that exposures to a prevalent environmental contaminant compromises the function of a key regulatory factor in erythropoiesis, producing effects functionally similar to inherited GATA-1 mutations. These findings highlight a novel molecular mechanism by which arsenic exposure may cause anemia and provide critical insights into potential prevention and intervention for arsenic-related anemias.

scholarly journals Kid-1, a putative renal transcription factor: regulation during ontogeny and in response to ischemia and toxic injury

1993 ◽  
Vol 13 (3) ◽  
pp. 1933-1942
Author(s):  
R Witzgall ◽  
E O'Leary ◽  
R Gessner ◽  
A J Ouellette ◽  
J V Bonventre
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Rat Kidney ◽  
Zinc Fingers ◽  
Simian Virus 40 ◽  
Regulation Of Transcription ◽  
Mrna Levels ◽  
Zinc Finger Region ◽  
In Cells

We have identified a new putative transcription factor from the rat kidney, termed Kid-1 (for kidney, ischemia and developmentally regulated gene 1). Kid-1 belongs to the C2H2 class of zinc finger genes. Its mRNA accumulates with age in postnatal renal development and is detected predominantly in the kidney. Kid-1 mRNA levels decline after renal injury secondary to ischemia or folic acid administration, two insults which result in epithelial cell dedifferentiation, followed by regenerative hyperplasia and differentiation. The low expression of Kid-1 early in postnatal development, and when renal tissue is recovering after injury, suggests that the gene product is involved in establishment of a differentiated phenotype and/or regulation of the proliferative response. The deduced protein contains 13 C2H2 zinc fingers at the COOH end in groups of 4 and 9 separated by a 32-amino-acid spacer. There are consensus sites for phosphorylation in the NH2 terminus non-zinc finger region as well as in the spacer region between zinc fingers 4 and 5. A region of the deduced protein shares extensive homology with a catalytic region of Raf kinases, a feature shared only with TFIIE among transcription factors. To determine whether Kid-1 can modulate transcription, a chimeric construct encoding the Kid-1 non-zinc finger region (sense or antisense) and the DNA-binding region of GAL4 was transfected into COS and LLC-PK1 cells together with a chloramphenicol acetyltransferase (CAT) reporter plasmid containing GAL4 binding sites, driven by either a minimal promoter or a simian virus 40 enhancer. CAT activity was markedly inhibited in cells transfected with the sense construct compared with the activity in cells transfected with the antisense construct. To our knowledge, this pattern of developmental regulation, kidney expression, and regulation of transcription is unique among the C2H2 class of zinc finger-containing DNA-binding proteins.

Interaction of Sp1 zinc finger with transport factor in the nuclear localization of transcription factor Sp1

2010 ◽  
Vol 403 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Tatsuo Ito ◽  
Haruka Kitamura ◽  
Chisana Uwatoko ◽  
Makiko Azumano ◽  
Kohji Itoh ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Nuclear Localization ◽  
Transport Factor ◽  
Transcription Factor Sp1

scholarly journals Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core.

1994 ◽  
Vol 14 (3) ◽  
pp. 1786-1795 ◽  
Author(s):  
J F Morris ◽  
R Hromas ◽  
F J Rauscher
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Binding Sites ◽  
Zinc Fingers ◽  
Consensus Sequences ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Gel Shift ◽  
Myeloid Zinc Finger

The myeloid zinc finger gene 1, MZF1, encodes a transcription factor which is expressed in hematopoietic progenitor cells that are committed to myeloid lineage differentiation. MZF1 contains 13 C2H2 zinc fingers arranged in two domains which are separated by a short glycine- and proline-rich sequence. The first domain consists of zinc fingers 1 to 4, and the second domain is formed by zinc fingers 5 to 13. We have determined that both sets of zinc finger domains bind DNA. Purified, recombinant MZF1 proteins containing either the first set of zinc fingers or the second set were prepared and used to affinity select DNA sequences from a library of degenerate oligonucleotides by using successive rounds of gel shift followed by PCR amplification. Surprisingly, both DNA-binding domains of MZF1 selected similar DNA-binding consensus sequences containing a core of four or five guanine residues, reminiscent of an NF-kappa B half-site: 1-4, 5'-AGTGGGGA-3'; 5-13, 5'-CGGGnGAGGGGGAA-3'. The full-length MZF1 protein containing both sets of zinc finger DNA-binding domains recognizes synthetic oligonucleotides containing either the 1-4 or 5-13 consensus binding sites in gel shift assays. Thus, we have identified the core DNA consensus binding sites for each of the two DNA-binding domains of a myeloid-specific zinc finger transcription factor. Identification of these DNA-binding sites will allow us to identify target genes regulated by MZF1 and to assess the role of MZF1 as a transcriptional regulator of hematopoiesis.

scholarly journals Kid-1, a putative renal transcription factor: regulation during ontogeny and in response to ischemia and toxic injury.

1993 ◽  
Vol 13 (3) ◽  
pp. 1933-1942 ◽  
Author(s):  
R Witzgall ◽  
E O'Leary ◽  
R Gessner ◽  
A J Ouellette ◽  
J V Bonventre
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Rat Kidney ◽  
Zinc Fingers ◽  
Simian Virus 40 ◽  
Regulation Of Transcription ◽  
Mrna Levels ◽  
Zinc Finger Region ◽  
In Cells

We have identified a new putative transcription factor from the rat kidney, termed Kid-1 (for kidney, ischemia and developmentally regulated gene 1). Kid-1 belongs to the C2H2 class of zinc finger genes. Its mRNA accumulates with age in postnatal renal development and is detected predominantly in the kidney. Kid-1 mRNA levels decline after renal injury secondary to ischemia or folic acid administration, two insults which result in epithelial cell dedifferentiation, followed by regenerative hyperplasia and differentiation. The low expression of Kid-1 early in postnatal development, and when renal tissue is recovering after injury, suggests that the gene product is involved in establishment of a differentiated phenotype and/or regulation of the proliferative response. The deduced protein contains 13 C2H2 zinc fingers at the COOH end in groups of 4 and 9 separated by a 32-amino-acid spacer. There are consensus sites for phosphorylation in the NH2 terminus non-zinc finger region as well as in the spacer region between zinc fingers 4 and 5. A region of the deduced protein shares extensive homology with a catalytic region of Raf kinases, a feature shared only with TFIIE among transcription factors. To determine whether Kid-1 can modulate transcription, a chimeric construct encoding the Kid-1 non-zinc finger region (sense or antisense) and the DNA-binding region of GAL4 was transfected into COS and LLC-PK1 cells together with a chloramphenicol acetyltransferase (CAT) reporter plasmid containing GAL4 binding sites, driven by either a minimal promoter or a simian virus 40 enhancer. CAT activity was markedly inhibited in cells transfected with the sense construct compared with the activity in cells transfected with the antisense construct. To our knowledge, this pattern of developmental regulation, kidney expression, and regulation of transcription is unique among the C2H2 class of zinc finger-containing DNA-binding proteins.

scholarly journals Structures of Zinc Finger Domains from Transcription Factor Sp1

1997 ◽  
Vol 272 (12) ◽  
pp. 7801-7809 ◽  
Author(s):  
Vaibhav A. Narayan ◽  
Richard W. Kriwacki ◽  
John P. Caradonna
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Transcription Factor Sp1 ◽  
Zinc Finger Domains

scholarly journals DNA-binding miniproteins based on zinc fingers. Assessment of the interaction using nanopores

2018 ◽  
Vol 9 (17) ◽  
pp. 4118-4123 ◽  
Author(s):  
Jéssica Rodríguez ◽  
Soraya Learte-Aymamí ◽  
Jesús Mosquera ◽  
Garbiñe Celaya ◽  
David Rodríguez-Larrea ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Fingers ◽  
Force Spectroscopy ◽  
High Affinity

We report a synthetic miniprotein that combines zinc finger modules of the transcription factor GAGA with the AT-hook peptide. This designed chimera binds to extended DNA sites with high affinity and selectivity, as shown by nanopore force spectroscopy.

Osteoclast-Derived Zinc Finger (OCZF) Protein With POZ Domain, a Possible Transcriptional Repressor, Is Involved in Osteoclastogenesis

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1987-1997 ◽  
Author(s):  
Akiko Kukita ◽  
Toshio Kukita ◽  
Mamoru Ouchida ◽  
Hidefumi Maeda ◽  
Hitomi Yatsuki ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Zinc Fingers ◽  
Related Factor ◽  
Kidney Cells ◽  
Nuclear Targeting ◽  
Consensus Sequences ◽  
Multinucleated Cells ◽  
High Level

Abstract The differentiation of osteoclasts is regulated by transcription factors expressed in cells of osteoclast lineage. We isolated here a potential transcription factor from a cDNA library of an enriched population of preosteoclasts and osteoclasts. The cDNA encodes a protein with N-terminal POZ domain and C-terminalKrüppel-like zinc fingers. We designate this protein as osteoclast-derived zinc finger (OCZF). OCZF was found to be rat homologue of mouse leukemia/lymphoma-related factor (LRF). Northern blot and in situ hybridization analysis showed OCZF mRNA at a high level in osteoclasts and kidney cells. OCZF had a nuclear targeting sequence and was localized in the nucleus of transfected cells. In addition, OCZF specifically bound to the guanine-rich consensus sequences of Egr-1 and c-Krox. Transient transfection assays indicate that OCZF can repress transcription activity like other POZ domain proteins. Furthermore, antisense but not sense phosphorothioate oligodeoxynucleotides (ODNs) for OCZF cDNA suppressed the formation of osteoclast-like multinucleated cells (MNCs) in bone marrow culture, whereas the same ODNs did not significantly affect the formation of macrophage polykaryons and mononuclear preosteoclast-like cells (POCs). These results suggest that OCZF is a unique transcription factor that plays an important role in the late stage of osteoclastogenesis.

Role of zinc finger structure in nuclear localization of transcription factor Sp1

2009 ◽  
Vol 380 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Tatsuo Ito ◽  
Makiko Azumano ◽  
Chisana Uwatoko ◽  
Kohji Itoh ◽  
Jun Kuwahara
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Nuclear Localization ◽  
Transcription Factor Sp1
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