scholarly journals Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene.

1992 ◽  
Vol 12 (12) ◽  
pp. 5632-5639 ◽  
Author(s):  
J G Kim ◽  
L D Hudson
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Chelating Agent ◽  
Proteolipid Protein ◽  
Polymerase Chain Reaction Analysis ◽  
Regulatory Elements ◽  
Binding Activity ◽  
Order Structure ◽  
Specific Gene ◽  
Sequence Comparisons

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.

Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene

1992 ◽  
Vol 12 (12) ◽  
pp. 5632-5639
Author(s):  
J G Kim ◽  
L D Hudson
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Chelating Agent ◽  
Proteolipid Protein ◽  
Polymerase Chain Reaction Analysis ◽  
Regulatory Elements ◽  
Binding Activity ◽  
Order Structure ◽  
Specific Gene ◽  
Sequence Comparisons

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.

scholarly journals Differentiation-Induced Cleavage of Cutl1/CDP Generates a Novel Dominant-Negative Isoform That Regulates Mammary Gene Expression

2006 ◽  
Vol 26 (20) ◽  
pp. 7466-7478 ◽  
Author(s):  
Urmila Maitra ◽  
Jin Seo ◽  
Mary M. Lozano ◽  
Jaquelin P. Dudley
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Late Pregnancy ◽  
Regulatory Elements ◽  
Binding Activity ◽  
Dominant Negative ◽  
Full Length ◽  
Cysteine Protease Inhibitor ◽  
Specific Gene ◽  
C Terminus

ABSTRACT Cutl1/CCAAT displacement protein (CDP) is a transcriptional repressor of mouse mammary tumor virus (MMTV), a betaretrovirus that is a paradigm for mammary-specific gene regulation. Virgin mammary glands have high levels of full-length CDP (200 kDa) that binds to negative regulatory elements (NREs) to repress MMTV transcription. During late pregnancy, full-length CDP levels decline, and a 150-kDa form of CDP (CDP150) appears concomitantly with a decline in DNA-binding activity for the MMTV NREs and an increase in viral transcripts. Developmental regulation of CDP was recapitulated in the normal mammary epithelial line, SCp2. Western blotting of tissue and SCp2 nuclear extracts confirmed that CDP150 lacks the C terminus. Transfection of tagged full-length and mutant cDNAs into SCp2 cells and use of a cysteine protease inhibitor demonstrated that CDP is proteolytically processed within the homeodomain to remove the C terminus during differentiation. Mixing of virgin and lactating mammary extracts or transfection of mutant CDP cDNAs missing the homeodomain into cells containing full-length CDP also abrogated NRE binding. Loss of DNA binding correlated with increased expression of MMTV and other mammary-specific genes, indicating that CDP150 is a developmentally induced dominant-negative protein. Thus, a novel posttranslational process controls Cutl1/CDP activity and gene expression in the mammary gland.

scholarly journals The Human Monocytic Leukemia Zinc Finger Histone Acetyltransferase Domain Contains DNA-binding Activity Implicated in Chromatin Targeting

2007 ◽  
Vol 282 (50) ◽  
pp. 36603-36613 ◽  
Author(s):  
Marc A. Holbert ◽  
Timothy Sikorski ◽  
Juliana Carten ◽  
Danielle Snowflack ◽  
Santosh Hodawadekar ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Histone Acetyltransferase ◽  
Binding Activity ◽  
Monocytic Leukemia ◽  
Dna Binding Activity ◽  
Human Monocytic Leukemia ◽  
Acetyltransferase Domain

Characterization of the DNA Binding Activity of the ZFY Zinc Finger Domain

Biochemistry ◽  
2010 ◽  
Vol 49 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jennifer Grants ◽  
Erin Flanagan ◽  
Andrea Yee ◽  
Paul J. Romaniuk
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Binding Activity ◽  
Zinc Finger Domain ◽  
Dna Binding Activity

Only two of the five zinc fingers of the eukaryotic transcriptional repressor PRDI-BF1 are required for sequence-specific DNA binding

1992 ◽  
Vol 12 (5) ◽  
pp. 1940-1949
Author(s):  
A D Keller ◽  
T Maniatis
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Specific Binding ◽  
Regulatory Element ◽  
Zinc Fingers ◽  
Transcriptional Repressor ◽  
Gene Promoter ◽  
Binding Activity ◽  
Necessary And Sufficient ◽  
Sequence Requirements

The eukaryotic transcriptional repressor PRDI-BF1 contains five zinc fingers of the C2H2 type, and the protein binds specifically to PRDI, a 14-bp regulatory element of the beta interferon gene promoter. We have investigated the amino acid sequence requirements for specific binding to PRDI and found that the five zinc fingers and a short stretch of amino acids N terminal to the first finger are necessary and sufficient for PRDI-specific binding. The contribution of individual zinc fingers to DNA binding was investigated by inserting them in various combinations into another zinc finger-containing DNA-binding protein whose own fingers had been removed. We found that insertion of PRDI-BF1 zinc fingers 1 and 2 confer PRDI-binding activity on the recipient protein. In contrast, the insertion of PRDI-BF1 zinc fingers 2 through 5, the insertion of zinc finger 1 or 2 alone, and the insertion of zinc fingers 1 and 2 in reverse order did not confer PRDI-binding activity. We conclude that the first two PRDI-BF1 zinc fingers together are sufficient for the sequence-specific recognition of PRDI.

scholarly journals Identification, nuclear localization, and DNA-binding activity of the zinc finger protein encoded by the Evi-1 myeloid transforming gene.

1990 ◽  
Vol 10 (3) ◽  
pp. 1259-1264 ◽  
Author(s):  
T Matsugi ◽  
K Morishita ◽  
J N Ihle
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Nuclear Protein ◽  
Zinc Finger Protein ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Double Stranded Dna ◽  
Finger Protein ◽  
Myeloid Leukemias ◽  
Transforming Gene

Activation of the Evi-1 zinc finger gene is a common event associated with transformation of murine myeloid leukemias. To characterize the gene product, we developed antisera against various protein domains. These antisera primarily detected a 145-kilodalton nuclear protein that bound double-stranded DNA. Binding was inhibited by chelating agents and partially restored by zinc ions.

scholarly journals An unusual arrangement of 13 zinc fingers in the vertebrate gene Z13

1995 ◽  
Vol 311 (1) ◽  
pp. 219-224 ◽  
Author(s):  
T C Schulz ◽  
B Hopwood ◽  
P D Rathjen ◽  
J R Wells
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Structural Organization ◽  
Zinc Fingers ◽  
Binding Activity ◽  
Protein Domain ◽  
Nucleic Acid Binding ◽  
C Terminus ◽  
Wide Range

The zinc finger is a protein domain that imparts specific nucleic acid-binding activity on a wide range of functionally important proteins. In this paper we report the molecular cloning and characterization of a novel murine zinc-finger gene, mZ13. Analysis of mZ13 cDNAs revealed that the gene expresses a 794-amino-acid protein encoded by a 2.7 kb transcript. The protein has an unusual arrangement of 13 zinc fingers into a ‘hand’ of 12 tandem fingers and a single isolated finger near the C-terminus. This structural organization is conserved with the probable chicken homologue, cZ13. mZ13 also contained an additional domain at the N-terminus which has previously been implicated in the regulation of zinc-finger transcription factor DNA-binding, via protein-protein interactions. mZ13 expression was detected in a wide range of murine embryonic and adult tissues. The structural organization of mZ13 and its expression profile suggest that it may function as a housekeeping DNA-binding protein that regulates the expression of specific genes.

scholarly journals The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins.

1994 ◽  
Vol 14 (12) ◽  
pp. 8292-8303 ◽  
Author(s):  
A Molnár ◽  
K Georgopoulos
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Ectopic Expression ◽  
Regulatory Elements ◽  
Lymphocyte Development ◽  
Sequence Specificity ◽  
Alternate Splicing ◽  
Gene Encoding ◽  
Regulatory Pathways ◽  
Functionally Diverse

We previously described the lymphocyte-restricted Ikaros gene encoding a zinc finger DNA-binding protein as a potential regulator of lymphocyte commitment and differentiation. Here, we report the isolation of four additional Ikaros transcripts, products of alternate splicing that encode functionally diverse proteins. The Ikaros proteins contain unique combinations of zinc finger modules that dictate their overall sequence specificity and affinity. The Ik-1 and Ik-2 proteins can both bind, albeit with different affinities, to the same recognition sequences present in a number of lymphocyte-specific regulatory elements. The Ik-3 and the Ik-4 proteins interact only with a subset of these motifs. The Ik-1 and Ik-2 proteins can strongly stimulate transcription, whereas Ik-3 and Ik-4 are weak activators. Significantly, the transcription activation potential of the Ikaros proteins correlates with their subcellular localization. Upon ectopic expression of the Ikaros isoforms in nonlymphoid cells, Ik-1 and Ik-2 localize to the nucleus, whereas Ik-3 and Ik-4 are predominantly found in the cytoplasm. The Ikaros isoforms are expressed differentially in lymphocytes: Ik-1 and Ik-2 mRNAs are the predominating forms, and Ik-4 is present in significant amounts only in early T-cell progenitors, whereas Ik-3 and Ik-5 transcripts are expressed at relatively low levels throughout lymphocyte development. The ability of the Ikaros gene to generate functionally diverse proteins that may participate in distinct regulatory pathways substantiates its role as a master regulator during lymphocyte development.

scholarly journals Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Krüppel-like factor: identification of a new multigene family.

1995 ◽  
Vol 15 (11) ◽  
pp. 5957-5965 ◽  
Author(s):  
K P Anderson ◽  
C B Kern ◽  
S C Crable ◽  
J B Lingrel
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Zinc Finger ◽  
Reporter Gene ◽  
Zinc Finger Protein ◽  
Erythroid Cell ◽  
Specific Gene ◽  
Beta Globin ◽  
Gene Encoding ◽  
Hybridization Probe

We have identified and characterized the gene for a novel zinc finger transcription factor which we have termed lung Krüppel-like factor (LKLF). LKLF was isolated through the use of the zinc finger domain of erythroid Krüppel-like factor (ELKF) as a hybridization probe and is closely related to this erythroid cell-specific gene. LKLF is expressed in a limited number of tissues, with the predominant expression seen in the lungs and spleen. The gene is developmentally controlled, with expression noted in the 7-day embryo followed by a down-regulation at 11 days and subsequent reactivation. A high degree of similarity is noted in the zinc finger regions of LKLF and EKLF. Beyond this domain, the sequences diverge significantly, although the putative transactivation domains for both LKLF and EKLF are proline-rich regions. In the DNA-binding domain, the three zinc finger motifs are so closely conserved that the predicted DNA contact sites are identical, suggesting that both proteins may bind to the same core sequence. This was further suggested by transactivation assays in which mouse fibroblasts were transiently transfected with a human beta-globin reporter gene in the absence and presence of an LKLF cDNA construct. Expression of the LKLF gene activates this human beta-globin promoter containing the CACCC sequence previously shown to be a binding site for EKLF. Mutation of this potential binding site results in a significant reduction in the reporter gene expression. LKLF and EKLF can thus be grouped as members of a unique family of transcription factors which have discrete patterns of expression in different tissues and which appear to recognize the same DNA-binding site.

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