scholarly journals Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif

2010 ◽  
Vol 285 (34) ◽  
pp. 25875-25879 ◽  
Author(s):  
Marina I. Siponen ◽  
Magdalena Wisniewska ◽  
Lari Lehtiö ◽  
Ida Johansson ◽  
Linda Svensson ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
B Cell ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Functional Domains ◽  
Structural Determination ◽  
Early B Cell Factor

scholarly journals B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits

1991 ◽  
Vol 11 (2) ◽  
pp. 1156-1160
Author(s):  
C Murre ◽  
A Voronova ◽  
D Baltimore
Keyword(s):  
Dna Binding ◽  
B Cell ◽  
Dna Sequence ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Dimerization Domain ◽  
Drosophila Development ◽  
Helix Loop Helix ◽  
Nuclear Factors ◽  
Biochemical Function

Recent studies have identified a family of DNA-binding proteins that share a common DNA-binding and dimerization domain with the potential to form a helix-loop-helix (HLH) structure. Various HLH proteins can form heterodimers that bind to a common DNA sequence, termed the E2-box. We demonstrate here that E2-box-binding B-cell- and myocyte-specific nuclear factors contain subunits which are identical or closely related to ubiquitously expressed (E12/E47) HLH proteins. These biochemical function for E12/E47-like molecules in mammalian differentiation, similar to the genetically defined function of daughterless in Drosophila development.

scholarly journals Photoaffinity labeling of transcription factors by DNA-templated crosslinking

2015 ◽  
Vol 6 (1) ◽  
pp. 745-751 ◽  
Author(s):  
Ying Liu ◽  
Wenlu Zheng ◽  
Wan Zhang ◽  
Nan Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Site ◽  
Binding Proteins ◽  
Photoaffinity Labeling ◽  
Dna Binding Proteins ◽  
Probe System ◽  
Dual Probe

A dual-probe system can specifically capture DNA-binding proteins with an unmodified binding site.

scholarly journals Regulation of Transcription by Hypoxia Requires a Multiprotein Complex That Includes Hypoxia-Inducible Factor 1, an Adjacent Transcription Factor, and p300/CREB Binding Protein

1998 ◽  
Vol 18 (7) ◽  
pp. 4089-4096 ◽  
Author(s):  
Benjamin L. Ebert ◽  
H. Franklin Bunn
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Binding Proteins ◽  
Binding Protein ◽  
Hypoxia Inducible Factor ◽  
Dna Binding Proteins ◽  
Creb Binding Protein ◽  
Multiprotein Complex ◽  
Hypoxia Inducible Factor 1

ABSTRACT Molecular adaptation to hypoxia depends on the binding of hypoxia-inducible factor 1 (HIF-1) to cognate response elements in oxygen-regulated genes. In addition, adjacent sequences are required for hypoxia-inducible transcription. To investigate the mechanism of interaction between these cis-acting sequences, the multiprotein complex binding to the lactate dehydrogenase A (LDH-A) promoter was characterized. The involvement of HIF-1, CREB-1/ATF-1, and p300/CREB binding protein (CBP) was demonstrated by techniques documenting in vitro binding, in combination with transient transfections that test the in vivo functional importance of each protein. In both the LDH-A promoter and the erythropoietin 3′ enhancer, formation of multiprotein complexes was analyzed by using biotinylated probes encompassing functionally critical cis-acting sequences. Strong binding of p300/CBP required interactions with multiple DNA binding proteins. Thus, the necessity of transcription factor binding sites adjacent to a HIF-1 site for hypoxically inducible transcription may be due to the requirement of p300 to interact with multiple transcription factors for high-affinity binding and activation of transcription. Since it has been found to interact with a wide range of transcription factors, p300 is likely to play a similar role in other genes, mediating interactions between DNA binding proteins, thereby activating stimulus-specific and tissue-specific gene transcription.

The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation

2010 ◽  
Vol 43 (1) ◽  
pp. 1-21 ◽  
Author(s):  
Aaron Klug
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Zinc Finger ◽  
Binding Proteins ◽  
Zinc Fingers ◽  
Dna Binding Proteins ◽  
Functional Domains ◽  
Control Of Gene Expression ◽  
Activation Domains ◽  
Finger Peptides

AbstractA long-standing goal of molecular biologists has been to construct DNA-binding proteins for the control of gene expression. The classical Cys2His2 (C2H2) zinc finger design is ideally suited for such purposes. Discriminating between closely related DNA sequences both in vitro and in vivo, this naturally occurring design was adopted for engineering zinc finger proteins (ZFPs) to target genes specifically.Zinc fingers were discovered in 1985, arising from the interpretation of our biochemical studies on the interaction of the Xenopus protein transcription factor IIIA (TFIIIA) with 5S RNA. Subsequent structural studies revealed its three-dimensional structure and its interaction with DNA. Each finger constitutes a self-contained domain stabilized by a zinc (Zn) ion ligated to a pair of cysteines and a pair of histidines and also by an inner structural hydrophobic core. This discovery showed not only a new protein fold but also a novel principle of DNA recognition. Whereas other DNA-binding proteins generally make use of the 2-fold symmetry of the double helix, functioning as homo- or heterodimers, zinc fingers can be linked linearly in tandem to recognize nucleic acid sequences of varying lengths. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA (or RNA). It is therefore not surprising that the zinc finger is found widespread in nature, including 3% of the genes of the human genome.The zinc finger design can be used to construct DNA-binding proteins for specific intervention in gene expression. By fusing selected zinc finger peptides to repression or activation domains, genes can be selectively switched off or on by targeting the peptide to the desired gene target. It was also suggested that by combining an appropriate zinc finger peptide with other effector or functional domains, e.g. from nucleases or integrases to form chimaeric proteins, genomes could be modified or manipulated.The first example of the power of the method was published in 1994 when a three-finger protein was constructed to block the expression of a human oncogene transformed into a mouse cell line. The same paper also described how a reporter gene was activated by targeting an inserted 9-base pair (bp) sequence, which acts as the promoter. Thus, by fusing zinc finger peptides to repression or activation domains, genes can be selectively switched off or on. It was also suggested that, by combining zinc fingers with other effector or functional domains, e.g. from nucleases or integrases, to form chimaeric proteins, genomes could be manipulated or modified.Several applications of such engineered ZFPs are described here, including some of therapeutic importance, and also their adaptation for breeding improved crop plants.

scholarly journals Natural selection driven by DNA binding proteins shapes genome-wide motif statistics

2016 ◽  
Author(s):  
Long Qian ◽  
Edo Kussell
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Large Collection ◽  
Functional Sites ◽  
Genome Wide ◽  
A Genome ◽  
Global Selection

AbstractEctopic DNA binding by transcription factors and other DNA binding proteins can be detrimental to cellular functions and ultimately to organismal fitness. The frequency of protein-DNA binding at non-functional sites depends on the global composition of a genome with respect to all possible short motifs, or k-mer words. To determine whether weak yet ubiquitous protein-DNA interactions could exert significant evolutionary pressures on genomes, we correlate in vitro measurements of binding strengths on all 8-mer words from a large collection of transcription factors, in several different species, against their relative genomic frequencies. Our analysis reveals a clear signal of purifying selection to reduce the large number of weak binding sites genome-wide. This evolutionary process, which we call global selection, has a detectable hallmark in that similar words experience similar evolutionary pressure, a consequence of the biophysics of protein-DNA binding. By analyzing a large collection of genomes, we show that global selection exists in all domains of life, and operates through tiny selective steps, maintaining genomic binding landscapes over long evolutionary timescales.

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