scholarly journals Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters

1992 ◽  
Vol 12 (7) ◽  
pp. 3273-3287
Author(s):  
A J van Wijnen ◽  
F M van den Ent ◽  
J B Lian ◽  
J L Stein ◽  
G S Stein
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Dna Binding ◽  
Consensus Sequence ◽  
Proximal Promoter ◽  
Gene Promoters ◽  
Histone H4 ◽  
Dna Interactions ◽  
Protein Dna Interactions ◽  
Diploid Cells

Transcriptional regulation of vertebrate histone genes during the cell cycle is mediated by several factors interacting with a series of cis-acting elements located in the 5' regions of these genes. The arrangement of these promoter elements is different for each gene. However, most histone H4 gene promoters contain a highly conserved sequence immediately upstream of the TATA box (H4 subtype consensus sequence), and this region in the human H4 gene FO108 is involved in cell cycle control. The sequence-specific interaction of nuclear factor HiNF-D with this key proximal promoter element of the H4-FO108 gene is cell cycle regulated in normal diploid cells (J. Holthuis, T.A. Owen, A.J. van Wijnen, K.L. Wright, A. Ramsey-Ewing, M.B. Kennedy, R. Carter, S.C. Cosenza, K.J. Soprano, J.B. Lian, J.L. Stein, and G.S. Stein, Science, 247:1454-1457, 1990). Here, we show that this region of the H4-FO108 gene represents a composite protein-DNA interaction domain for several distinct sequence-specific DNA-binding activities, including HiNF-D, HiNF-M, and HiNF-P. Factor HiNF-P is similar to H4TF-2, a DNA-binding activity that is not cell cycle regulated and that interacts with the analogous region of the H4 gene H4.A (F. LaBella and N. Heintz, Mol. Cell. Biol. 11:5825-5831, 1991). The H4.A gene fails to interact with factors HiNF-M and HiNF-D owing to two independent sets of specific nucleotide variants, indicating differences in protein-DNA interactions between these H4 genes. Cytosine methylation of a highly conserved CpG dinucleotide interferes with binding of HiNF-P/H4TF-2 to both the H4-FO108 and H4.A promoters, but no effect is observed for either HiNF-M or HiNF-D binding to the H4-FO108 gene. Thus, strong evolutionary conservation of the H4 consensus sequence may be related to combinatorial interactions involving overlapping and interdigitated recognition nucleotides for several proteins, whose activities are regulated independently. Our results also suggest molecular complexity in the transcriptional regulation of distinct human H4 genes.

scholarly journals Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters.

1992 ◽  
Vol 12 (7) ◽  
pp. 3273-3287 ◽  
Author(s):  
A J van Wijnen ◽  
F M van den Ent ◽  
J B Lian ◽  
J L Stein ◽  
G S Stein
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Dna Binding ◽  
Consensus Sequence ◽  
Proximal Promoter ◽  
Gene Promoters ◽  
Histone H4 ◽  
Dna Interactions ◽  
Protein Dna Interactions ◽  
Diploid Cells

Transcriptional regulation of vertebrate histone genes during the cell cycle is mediated by several factors interacting with a series of cis-acting elements located in the 5' regions of these genes. The arrangement of these promoter elements is different for each gene. However, most histone H4 gene promoters contain a highly conserved sequence immediately upstream of the TATA box (H4 subtype consensus sequence), and this region in the human H4 gene FO108 is involved in cell cycle control. The sequence-specific interaction of nuclear factor HiNF-D with this key proximal promoter element of the H4-FO108 gene is cell cycle regulated in normal diploid cells (J. Holthuis, T.A. Owen, A.J. van Wijnen, K.L. Wright, A. Ramsey-Ewing, M.B. Kennedy, R. Carter, S.C. Cosenza, K.J. Soprano, J.B. Lian, J.L. Stein, and G.S. Stein, Science, 247:1454-1457, 1990). Here, we show that this region of the H4-FO108 gene represents a composite protein-DNA interaction domain for several distinct sequence-specific DNA-binding activities, including HiNF-D, HiNF-M, and HiNF-P. Factor HiNF-P is similar to H4TF-2, a DNA-binding activity that is not cell cycle regulated and that interacts with the analogous region of the H4 gene H4.A (F. LaBella and N. Heintz, Mol. Cell. Biol. 11:5825-5831, 1991). The H4.A gene fails to interact with factors HiNF-M and HiNF-D owing to two independent sets of specific nucleotide variants, indicating differences in protein-DNA interactions between these H4 genes. Cytosine methylation of a highly conserved CpG dinucleotide interferes with binding of HiNF-P/H4TF-2 to both the H4-FO108 and H4.A promoters, but no effect is observed for either HiNF-M or HiNF-D binding to the H4-FO108 gene. Thus, strong evolutionary conservation of the H4 consensus sequence may be related to combinatorial interactions involving overlapping and interdigitated recognition nucleotides for several proteins, whose activities are regulated independently. Our results also suggest molecular complexity in the transcriptional regulation of distinct human H4 genes.

Protein-DNA interactions at the H4-Site III upstream transcriptional element of a cell cycle regulated histone H4 gene: Differences in normal versus tumor cells

1992 ◽  
Vol 49 (1) ◽  
pp. 93-110 ◽  
Author(s):  
C. Willemien van der Houven van Oordt ◽  
Andre J. van Wijnen ◽  
Ruth Carter ◽  
Kenneth Soprano ◽  
Jane B. Lian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Cells ◽  
Histone H4 ◽  
Dna Interactions ◽  
Protein Dna Interactions ◽  
A Cell ◽  
Histone H4 Gene

scholarly journals Target Gene Specificity of E2F and Pocket Protein Family Members in Living Cells

2000 ◽  
Vol 20 (16) ◽  
pp. 5797-5807 ◽  
Author(s):  
Julie Wells ◽  
Kathryn E. Boyd ◽  
Christopher J. Fry ◽  
Stephanie M. Bartley ◽  
Peggy J. Farnham
Keyword(s):  
Cell Cycle ◽  
Target Gene ◽  
Target Genes ◽  
Protein Complexes ◽  
Current Model ◽  
Family Members ◽  
Living Cells ◽  
Gene Promoters ◽  
Pocket Protein ◽  
Protein Dna Interactions

ABSTRACT E2F-mediated transcription is thought to involve binding of an E2F-pocket protein complex to promoters in the G0 phase of the cell cycle and release of the pocket protein in late G1, followed by release of E2F in S phase. We have tested this model by monitoring protein-DNA interactions in living cells using a formaldehyde cross-linking and immunoprecipitation assay. We find that E2F target genes are bound by distinct E2F-pocket protein complexes which change as cells progress through the cell cycle. We also find that certain E2F target gene promoters are bound by pocket proteins when such promoters are transcriptionally active. Our data indicate that the current model applies only to certain E2F target genes and suggest that Rb family members may regulate transcription in both G0 and S phases. Finally, we find that a given promoter can be bound by one of several different E2F-pocket protein complexes at a given time in the cell cycle, suggesting that cell cycle-regulated transcription is a stochastic, not a predetermined, process.

scholarly journals Protein–DNA Interactions: The Story so Far and a New Method for Prediction

2003 ◽  
Vol 4 (4) ◽  
pp. 428-431 ◽  
Author(s):  
Susan Jones ◽  
Janet M. Thornton
Keyword(s):  
Dna Binding ◽  
Protein Structures ◽  
Accessible Surface Area ◽  
New Method ◽  
Dna Interactions ◽  
Binding Function ◽  
Protein Dna Interactions ◽  
Template Library ◽  
Accessible Surface ◽  
Complete Protein

This review describes methods for the prediction of DNA binding function, and specifically summarizes a new method using 3D structural templates. The new method features the HTH motif that is found in approximately one-third of DNAbinding protein families. A library of 3D structural templates of HTH motifs was derived from proteins in the PDB. Templates were scanned against complete protein structures and the optimal superposition of a template on a structure calculated. Significance thresholds in terms of a minimum root mean squared deviation (rmsd) of an optimal superposition, and a minimum motif accessible surface area (ASA), have been calculated. In this way, it is possible to scan the template library against proteins of unknown function to make predictions about DNA-binding functionality.

scholarly journals The geometric influence on the Cys2His2 zinc finger domain and functional plasticity

2020 ◽  
Vol 48 (11) ◽  
pp. 6382-6402
Author(s):  
April L Mueller ◽  
Carles Corbi-Verge ◽  
David O Giganti ◽  
David M Ichikawa ◽  
Jeffrey M Spencer ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Fingers ◽  
Binding Specificity ◽  
Synthetic Approach ◽  
Dna Interactions ◽  
Dna Binding Specificity ◽  
Mechanistic Insight ◽  
Natural Geometry ◽  
Protein Dna Interactions

Abstract The Cys2His2 zinc finger is the most common DNA-binding domain expanding in metazoans since the fungi human split. A proposed catalyst for this expansion is an arms race to silence transposable elements yet it remains poorly understood how this domain is able to evolve the required specificities. Likewise, models of its DNA binding specificity remain error prone due to a lack of understanding of how adjacent fingers influence each other's binding specificity. Here, we use a synthetic approach to exhaustively investigate binding geometry, one of the dominant influences on adjacent finger function. By screening over 28 billion protein–DNA interactions in various geometric contexts we find the plasticity of the most common natural geometry enables more functional amino acid combinations across all targets. Further, residues that define this geometry are enriched in genomes where zinc fingers are prevalent and specificity transitions would be limited in alternative geometries. Finally, these results demonstrate an exhaustive synthetic screen can produce an accurate model of domain function while providing mechanistic insight that may have assisted in the domains expansion.

scholarly journals TATA box-dependent protein-DNA interactions are detected on heat shock and histone gene promoters in nuclear extracts derived from Drosophila melanogaster embryos.

1988 ◽  
Vol 8 (8) ◽  
pp. 3204-3214 ◽  
Author(s):  
D S Gilmour ◽  
T J Dietz ◽  
S C Elgin
Keyword(s):  
Drosophila Melanogaster ◽  
Heat Shock ◽  
Transcriptional Activation ◽  
Tata Box ◽  
Gene Promoters ◽  
Dna Interactions ◽  
Nuclear Extracts ◽  
Protein Dna Interactions ◽  
Exonuclease Digestion

We monitored protein-DNA interactions that occur on the hsp26, hsp70, histone H3, and histone H4 promoters in nuclear extracts derived from frozen Drosophila melanogaster embryos. All four of these promoters were found to be transcribed in vitro at comparable levels by extracts from both heat-shocked and non-heat-shocked embryos. Factors were detected in both types of extracts that block exonuclease digestion from a downstream site at ca. +35 and -20 base pairs from the start of transcription of all four of these promoters. In addition, factors in extracts from heat-shocked embryos blocked exonuclease digestion at sites flanking the heat shock consensus sequences of hsp26 and hsp70. Competition experiments indicated that common factors cause the +35 and -20 barriers on all four promoters in both extracts. The formation of the barriers at +35 and -20 required a TATA box but did not appear to require specific sequences downstream of +7. We suggest that the factors responsible for the +35 and -20 barriers are components whose association with the promoter precedes transcriptional activation.

scholarly journals Molecular dynamics studies on the DNA-binding process of ERG

2016 ◽  
Vol 12 (12) ◽  
pp. 3600-3610 ◽  
Author(s):  
Matthias G. Beuerle ◽  
Neil P. Dufton ◽  
Anna M. Randi ◽  
Ian R. Gould
Keyword(s):  
Molecular Dynamics ◽  
Transcription Factor ◽  
Dna Binding ◽  
Sequence Specificity ◽  
Dna Interactions ◽  
Binding Process ◽  
Protein Dna Interactions

Molecular dynamics study elucidating the mechanistic background of the DNA-binding process and the sequence specificity of the transcription factor ERG. Along with the biological findings the capabilities of unbiased DNA-binding simulations in combination with various means of analysis in the field of protein DNA-interactions are shown.

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