ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene

1994 ◽  
Vol 14 (2) ◽  
pp. 1395-1401
Author(s):  
H Yasuda ◽  
A Mizuno ◽  
T Tamaoki ◽  
T Morinaga
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Human Albumin ◽  
Alpha Fetoprotein ◽  
Promoter Regions ◽  
Expression Plasmid ◽  
Zinc Finger Motifs ◽  
Transcriptional Regulatory ◽  
Cat Gene ◽  
Afp Promoter

ATBF1 is a 306-kDa protein containing four homeodomains, 17 zinc finger motifs, and several segments potentially involved in transcriptional regulation (T. Morinaga, H. Yasuda, T. Hashimoto, K. Higashio, and T. Tamaoki, Mol. Cell. Biol. 11:6041-6049, 1991). At least one of the homeodomains of ATBF1 binds to an AT-rich element in the human alpha-fetoprotein (AFP) enhancer (enhancer AT motif). In the present work, we analyzed the transcriptional regulatory activity of ATBF1 with respect to the enhancer AT motif and similar AT-rich elements in the human AFP promoter and the human albumin promoter and enhancer. Gel retardation assays showed that ATBF1 binds to the AFP enhancer AT motif efficiently; however, it binds weakly or not at all to other AT-rich elements in the AFP and albumin regulatory regions studied. Alterations of the enhancer AT motif by site-specific mutagenesis resulted in the loss of binding of ATBF1. Cotransfection experiments with an ATBF1 expression plasmid and the chloramphenicol acetyltransferase (CAT) gene fused to AFP promoter or enhancer fragments showed that ATBF1 suppressed the activity of AFP enhancer and promoter regions containing AT-rich elements. This suppression was reduced when the mutated AT motifs with low affinity to ATBF1 were linked to the CAT gene. The ATBF1 suppression of AFP promoter and enhancer activities appeared to be due, at least in part, to competition between ATBF1 and HNF1 for the same binding site. In contrast to the AFP promoter and enhancer, the albumin promoter and enhancer were not affected by ATBF1, although they contain homologous AT-rich elements. These results show that ATBF1 is able to distinguish AFP and albumin AT-rich elements, leading to selective suppression of the AFP promoter and enhancer activities.

scholarly journals ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.

1994 ◽  
Vol 14 (2) ◽  
pp. 1395-1401 ◽  
Author(s):  
H Yasuda ◽  
A Mizuno ◽  
T Tamaoki ◽  
T Morinaga
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Human Albumin ◽  
Alpha Fetoprotein ◽  
Promoter Regions ◽  
Expression Plasmid ◽  
Zinc Finger Motifs ◽  
Transcriptional Regulatory ◽  
Cat Gene ◽  
Afp Promoter

ATBF1 is a 306-kDa protein containing four homeodomains, 17 zinc finger motifs, and several segments potentially involved in transcriptional regulation (T. Morinaga, H. Yasuda, T. Hashimoto, K. Higashio, and T. Tamaoki, Mol. Cell. Biol. 11:6041-6049, 1991). At least one of the homeodomains of ATBF1 binds to an AT-rich element in the human alpha-fetoprotein (AFP) enhancer (enhancer AT motif). In the present work, we analyzed the transcriptional regulatory activity of ATBF1 with respect to the enhancer AT motif and similar AT-rich elements in the human AFP promoter and the human albumin promoter and enhancer. Gel retardation assays showed that ATBF1 binds to the AFP enhancer AT motif efficiently; however, it binds weakly or not at all to other AT-rich elements in the AFP and albumin regulatory regions studied. Alterations of the enhancer AT motif by site-specific mutagenesis resulted in the loss of binding of ATBF1. Cotransfection experiments with an ATBF1 expression plasmid and the chloramphenicol acetyltransferase (CAT) gene fused to AFP promoter or enhancer fragments showed that ATBF1 suppressed the activity of AFP enhancer and promoter regions containing AT-rich elements. This suppression was reduced when the mutated AT motifs with low affinity to ATBF1 were linked to the CAT gene. The ATBF1 suppression of AFP promoter and enhancer activities appeared to be due, at least in part, to competition between ATBF1 and HNF1 for the same binding site. In contrast to the AFP promoter and enhancer, the albumin promoter and enhancer were not affected by ATBF1, although they contain homologous AT-rich elements. These results show that ATBF1 is able to distinguish AFP and albumin AT-rich elements, leading to selective suppression of the AFP promoter and enhancer activities.

Zinc finger protein ZFP36L1 inhibits flavivirus infection by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways.

2021 ◽  
Author(s):  
Han Chiu ◽  
Hsin-Ping Chiu ◽  
Han-Pang Yu ◽  
Li-Hsiung Lin ◽  
Zih-Ping Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Viral Rna ◽  
Rna Decay ◽  
Finger Protein ◽  
Zinc Finger Motifs ◽  
Rna Exosome

Zinc-finger protein 36, CCCH type-like 1 (ZFP36L1), containing tandem CCCH-type zinc-finger motifs with an RNA-binding property, plays an important role in cellular RNA metabolism mainly via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 has potent antiviral activity against influenza A virus infection. However, its role in the host defense response against flaviviruses has not been addressed. Here, we demonstrate that ZFP36L1 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L1 reduced JEV and DENV infection, and ZFP36L1 knockdown enhanced viral replication. ZFP36L1 destabilized the JEV genome by targeting and degrading viral RNA mediated by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways. Mutation in both zinc-finger motifs of ZFP36L1 disrupted RNA-binding and antiviral activity. Furthermore, the viral RNA sequences specifically recognized by ZFP36L1 were mapped to the 3'-untranslated region of the JEV genome with the AU-rich element (AUUUA) motif. We extend the function of ZFP36L1 to host antiviral defense by directly binding and destabilizing the viral genome via recruiting cellular mRNA decay machineries. Importance Cellular RNA-binding proteins are among the first lines of defense against various viruses, particularly RNA viruses. ZFP36L1 belongs to the CCCH-type zinc-finger protein family and has RNA-binding activity; it has been reported to directly bind to the AU-rich elements (AREs) of a subset of cellular mRNAs and then lead to mRNA decay by recruiting mRNA degrading enzymes. However, the antiviral potential of ZFP36L1 against flaviviruses has not yet been fully demonstrated. Here, we reveal the antiviral potential of human ZFP36L1 against Japanese encephalitis virus (JEV) and dengue virus (DENV). ZFP36L1 specifically targeted the ARE motif within viral RNA and triggered the degradation of viral RNA transcripts via cellular degrading enzymes, 5′-3′ XRN1 and 3′-5′ RNA exosome. These findings provide mechanistic insights into how human ZFP36L1 serves as a host antiviral factor to restrict flavivirus replication.

A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers

1991 ◽  
Vol 11 (12) ◽  
pp. 6041-6049
Author(s):  
T Morinaga ◽  
H Yasuda ◽  
T Hashimoto ◽  
K Higashio ◽  
T Tamaoki
Keyword(s):  
Binding Protein ◽  
Zinc Fingers ◽  
Structural Features ◽  
Alpha Fetoprotein ◽  
Zinc Finger Motifs ◽  
Transcriptional Regulatory ◽  
Enhancer Binding Protein ◽  
Exact Function ◽  
Gene Enhancer ◽  
Number Of Segments

We have isolated a full-length cDNA encoding a protein (ATBF1) that binds to an AT-rich motif in the human alpha-fetoprotein gene enhancer. The amino acid sequence deduced from the cDNA revealed that this is the largest DNA-binding protein (306 kDa) known to date, containing four homeodomains, 17 zinc finger motifs, and a number of segments potentially involved in transcriptional regulation. Although the exact function of this protein has not been determined, these structural features suggest that ATBF1 plays a transcriptional regulatory role.

scholarly journals Transcriptional Activities of the Zinc Finger Protein Zac Are Differentially Controlled by DNA Binding

2003 ◽  
Vol 23 (3) ◽  
pp. 988-1003 ◽  
Author(s):  
Anke Hoffmann ◽  
Elisabetta Ciani ◽  
Joel Boeckardt ◽  
Florian Holsboer ◽  
Laurent Journot ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Zinc Fingers ◽  
Repeat Elements ◽  
Functional Connections ◽  
Finger Protein ◽  
Dna Binding Sites ◽  
Transcriptional Regulatory ◽  
Dna Elements

ABSTRACT Zac encodes a zinc finger protein that promotes apoptosis and cell cycle arrest and is maternally imprinted. Here, we show that Zac contains transactivation and repressor activities and that these transcriptional activities are differentially controlled by DNA binding. Zac transactivation mapped to two distinct domains. One of these contained multiple repeats of the peptide PLE, which behaved as an autonomous activation unit. More importantly, we identified two related high-affinity DNA-binding sites which were differentially bound by seven Zac C2H2 zinc fingers. Zac bound as a monomer through zinc fingers 6 and 7 to the palindromic DNA element to confer transactivation. In contrast, binding as a monomer to one half-site of the repeat element turned Zac into a repressor. Conversely, Zac dimerization at properly spaced direct and reverse repeat elements enabled transactivation, which strictly correlated with DNA-dependent and -independent contacts of key residues within the recognition helix of zinc finger 7. The later ones support specific functional connections between Zac DNA binding and transcriptional-regulatory surfaces. Both classes of DNA elements were identified in a new Zac target gene and confirmed that the zinc fingers communicate with the transactivation function. Together, our data demonstrate a role for Zac as a transcription factor in addition to its role as coactivator for nuclear receptors and p53.

scholarly journals PIAS1 interacts with the KRAB zinc finger protein, ZNF133, via zinc finger motifs and regulates its transcriptional activity

2007 ◽  
Vol 39 (4) ◽  
pp. 450-457 ◽  
Author(s):  
Sang-Jin Lee ◽  
Jae-Rin Lee ◽  
Hwa-Sun Hah ◽  
Young-Hoon Kim ◽  
Jin-Hyun Ahn ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activity ◽  
Zinc Finger Protein ◽  
Finger Protein ◽  
Zinc Finger Motifs

scholarly journals A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers.

1991 ◽  
Vol 11 (12) ◽  
pp. 6041-6049 ◽  
Author(s):  
T Morinaga ◽  
H Yasuda ◽  
T Hashimoto ◽  
K Higashio ◽  
T Tamaoki
Keyword(s):  
Binding Protein ◽  
Zinc Fingers ◽  
Structural Features ◽  
Alpha Fetoprotein ◽  
Zinc Finger Motifs ◽  
Transcriptional Regulatory ◽  
Enhancer Binding Protein ◽  
Exact Function ◽  
Gene Enhancer ◽  
Number Of Segments

We have isolated a full-length cDNA encoding a protein (ATBF1) that binds to an AT-rich motif in the human alpha-fetoprotein gene enhancer. The amino acid sequence deduced from the cDNA revealed that this is the largest DNA-binding protein (306 kDa) known to date, containing four homeodomains, 17 zinc finger motifs, and a number of segments potentially involved in transcriptional regulation. Although the exact function of this protein has not been determined, these structural features suggest that ATBF1 plays a transcriptional regulatory role.

Identification, Characterization of a Novel Zinc Finger Protein (HZF1) Gene and Its Roles in Erythroid Differentiation and Megakaryocyte Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4237-4237
Author(s):  
Jun-Wu Zhang ◽  
Han Peng ◽  
Zhan-Wen Du
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Structure Characterization ◽  
Megakaryocytic Differentiation ◽  
Cdna Sequences ◽  
Finger Protein ◽  
Zinc Finger Motifs

Abstract A significant number of transcription factors contain evolutionarily conserved zinc finger motifs. The classical C2H2 zinc finger motif, which employs two cysteine and two histidine residues to coordinate a single zinc ion, is a maim type of the zinc finger proteins. Many of the identified C2H2 type zinc protein have been demonstrated to be transcription factors that play important roles in differentiation and development of cells and tissues of higher organisms. In this study, we obtained some novel expression sequence tags (ESTs) containing C2H2 type motifs by reverse transcription-polymerase chain reaction (RT-PCR) using RNAs derived from hemin-induced K562 cells. A cDNA encoding novel zinc finger protein (designed as HZF1) was obtained by screening the human bone marrow cDNA library using one of the ESTs as the probe. The cDNA sequences (2013 nucleotides) have been submitted to the GenBank databases under accession No. AF244088.1). Three transcripts of HZF1 gene were explored by PCR amplification of cDNAs derived from hemin-induced K562 cells. The cDNA sequences (2632 nucleotides) of the longest transcript have been submitted to the GenBank databases under accession No. DQ117529). These transcripts may result from different splicing of the pre-mRNA of HZF1 but the differences between them are only involved in 5′ non-translation region of HZF1 mRNA. BLASTN analysis revealed that HZF1 gene has four exons and three introns. The putative protein consists of 670 amino acid residues including continuous 15 C2H2 and 2 C2RH zinc finger motifs. This structure characterization and the nuclear location of the protein suggest that HZF1 may function as a transcription factor. HZF1 mRNA was detected in ubiquitous tissues and various hematopoietic cell lines. Increased HZF1 mRNA expression was observed following hemin-induction or phorbol myristate acetate (PMA)-induction of K562 cells. Both of the antisence method and RNA interference assay revealed that repression of the intrinsic expression of HZF1 blocked the hemin-induced erythroid differentiation and reduced the PMA-induced megakaryocytic differentiation of K562 cells, which suggested that HZF1 play an important part in erythroid differentiation and megakaryocytic differentiation.

scholarly journals Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver

2008 ◽  
Vol 105 (31) ◽  
pp. 10859-10864 ◽  
Author(s):  
Z. Xie ◽  
H. Zhang ◽  
W. Tsai ◽  
Y. Zhang ◽  
Y. Du ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Gene Transcription ◽  
Zinc Finger Protein ◽  
Alpha Fetoprotein ◽  
Finger Protein

scholarly journals Sequence-Specific Transcriptional Repression by KS1, a Multiple-Zinc-Finger–Krüppel-Associated Box Protein

2001 ◽  
Vol 21 (3) ◽  
pp. 928-939 ◽  
Author(s):  
Brian Gebelein ◽  
Raul Urrutia
Keyword(s):  
Gene Expression ◽  
Zinc Finger ◽  
Dna Sequences ◽  
Transcriptional Repression ◽  
Zinc Finger Protein ◽  
Site Directed Mutagenesis ◽  
Linker Region ◽  
Krab Domain ◽  
C Terminus ◽  
Zinc Finger Motifs

ABSTRACT The vertebrate genome contains a large number of Krüppel-associated box–zinc finger genes that encode 10 or more C2-H2 zinc finger motifs. Members of this gene family have been proposed to function as transcription factors by binding DNA through their zinc finger region and repressing gene expression via the KRAB domain. To date, however, no Krüppel-associated box–zinc finger protein (KRAB-ZFP) and few proteins with 10 or more zinc finger motifs have been shown to bind DNA in a sequence-specific manner. Our laboratory has recently identified KS1, a member of the KRAB-ZFP family that contains 10 different C2-H2 zinc finger motifs, 9 clustered at the C terminus with an additional zinc finger separated by a short linker region. In this study, we used a random oligonucleotide binding assay to identify a 27-bp KS1 binding element (KBE). Reporter assays demonstrate that KS1 represses the expression of promoters containing this DNA sequence. Deletion and site-directed mutagenesis reveal that KS1 requires nine C-terminal zinc fingers and the KRAB domain for transcriptional repression through the KBE site, whereas the isolated zinc finger and linker region are dispensable for this function. Additional biochemical assays demonstrate that the KS1 KRAB domain interacts with the KAP-1 corepressor, and mutations that abolish this interaction alleviate KS1-mediated transcriptional repression. Thus, this study provides the first direct evidence that a KRAB-ZFP binds DNA to regulate gene expression and provides insight into the mechanisms used by multiple-zinc-finger proteins to recognize DNA sequences.

Sign in / Sign up

Export Citation Format

Share Document