Nucleotide recognition by histone H1 involves specific protein structures.
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Biomedical subjects
R M Mannermaa
Publications and source records attributed to R M Mannermaa.
Nucleotide recognition by histone H1 involves specific protein structures.
We have reported previously that histone H1 is capable of binding nucleotides such as ATP, GTP, ADP, and GDP in a specific manner. It is demonstrated here using labeling with the uv-crosslinkable ATP analog 8-azido-[alpha-32P]ATP that this ability is a unique characteristic of H1 among the histone proteins. Phosphate analogs such as AlF-4 efficiently counteract the labeling of H1, while they do not compete for labeling of histones H2A, H2B, H3, and H4. Consistent with the assumption that this labeling is due to specific binding, nucleotides competed for the labeling of H1 in a manner similar to labeling of the catalytic subunit of cAMP-dependent protein kinase, casein kinase-II, and heat shock protein-90, all of which are ATP/GTP-binding proteins. The site of nucleotide interaction was subsequently located in a Gly-rich region of H1 which displays homology with the protein kinases, using either radioactive labeling with nucleotide analogs and endoproteinase Glu-C digestion or synthetic peptides corresponding to the putative binding site. The results imply that specific protein structures are involved in nucleotide binding to H1 and that the ability of H1 to bind nucleotides may provide a mechanism for the regulation of eukaryotic gene expression.
Acetyl Coenzyme A↗
Specific non-enzymatic glycation of the rat histone H1 nucleotide binding site in vitro in the presence of AlF4-. A putative mechanism for impaired chromatin function.
We show here that an aluminium derivative, AlF4-, stimulates glycation of histone H1 selectively in the proximity of its nucleotide-binding site. This adduct formation interferes with nucleoside triphosphate hydrolysis by H1 and with nucleotide modulation of H1 DNA binding. The present mode of aluminium action may in part be responsible for its effects on the chromatin structure and expression of tissue-specific genes, and may constitute a mechanism in the pathogenesis of aluminium-induced encephalopathy and in that of Alzheimer's disease, for example.
Aluminum↗
DNA binding of histone H1 is modulated by nucleotides.
Histone H1 acts as a general repressor of transcription in eukaryotes by organizing nucleosomes into inaccessible condensed forms of chromatin. The capability of H1 to bind to DNA with some sequence specificity is likely to be critical in the control of these processes. We show here that ATP and several other nucleotides, including non-hydrolyzable derivatives, can inhibit DNA binding of H1. The results also show that ATP differentially affects binding of H1 to DNA in a fashion enhancing nucleotide sequence specificity of the binding. The study suggests a novel mechanism of modulation of H1 activity that has important implications for the role of H1 as a transcriptional regulator.
Amino Acid Sequence↗
Nucleoside triphosphate binding and hydrolysis by histone H1.
We present here further evidence supporting that histone H1 contains a nucleotide binding site interacting e.g. with ADP, ATP, GDP and GTP. The finding is in accordance with the previous observation that nucleotides modulate recognition of DNA by H1. Most interestingly, H1 appears to be capable of hydrolyzing NTPs and incorporating phosphate to exogenous proteins. The mode of nucleotide action on H1 may be considered highly analogous to that of GTPases. Nuclear receptors may thus act through mechanisms similar to those for receptors on the plasma membrane.
Acetyl Coenzyme A↗
Interference of AlF4- with nucleotide and DNA binding of rat histone H1 in vitro. Implications for the pathogenesis of Alzheimer's disease.
We demonstrate here that the H2PO4- analogue AlF4- binds to the nucleotide-binding site of rat liver histone H1 in vitro, and interferes with nucleotide recognition and H1 DNA binding. AlF4- may thus compromise the genetically determined pattern of protein synthesis through binding to H1, the general repressor. The present findings are of interest as a number of studies have implicated aluminium as a factor in the pathogenesis of Alzheimer's disease.
Aluminum↗
The histone H1-lacZ' fusion protein produced in Escherichia coli binds to the 5'-TTGGCAnnnTGCCAA-3' motif on DNA.
The coding region of the chicken histone H1.03 gene was cloned to a bacterial expression vector, and the 291-amino acid H1-beta-galactosidase fusion protein was isolated after induction with IPTG. The fusion protein recognizes the 5'-TTGGCAnnnTGCCAA-3' motif on DNA. The H1 globular domain was initially shown to be responsible for the sequence-specific binding by functional deletion analysis. This function may be indispensable for the role of H1 as a determinant of nucleosome positioning and as a eukaryotic repressor.
Animals↗
The predicted molecular structure suggests that CTF/NF-I may function as a histone acetylase.
The primary structure of nuclear factor-I (CTF/NF-I), a eukaryotic regulatory DNA-binding protein involved in both DNA replication and gene transcription, and the secondary structure predictable from it, are compared here with those of a number of prokaryotic acetylases. Hydropathy and Chou-Fasman analyses reveal that the polypeptide chain of CTF/NF-I is likely to fold to higher order structures similar to those of the acetylases, and significant conservation of functionally important regions of the acetylases is observed in CTF/NF-I. It is therefore suggested that CTF/NF-I may function as a histone acetylase.
Acetyltransferases↗
A DNA-binding homeodomain in histone H1.
The structure of the globular domain of chicken histone H1 was compared here with that of the DNA-binding homeodomain in the Drosophila Antp protein, and they were observed to display considerable similarity. Both of them consist of three or four alpha-helices separated by well-defined turns. Charged residues in the aminoterminal end of alpha 3 are therefore suggested to be responsible for sequence-specific recognition of DNA by the histone. In addition, alpha 2 of H1, with a short leucine zipper in it, may be capable of protein-protein interaction in a similar manner to the other homeodomains.
Amino Acid Sequence↗
Impairment of histone H1 DNA binding by adduct formation with acetaldehyde.
Incubation of histone H1 with pharmacologically relevant concentrations of acetaldehyde resulted in the formation of spontaneously stable acetaldehyde-protein linkages. The reaction of acetaldehyde and H1 purified from rat liver either by a DNA recognition site affinity chromatography or by perchloric acid extraction occurred primarily at the lysine residues in the carboxyterminal tail of H1, which is crucial for its function as a eukaryotic repressor. It was further shown using an H1-lacZ fusion protein produced in E. coli and the protein isolated from rat liver that the formation of acetaldehyde adducts with H1 impair its DNA binding properties. We propose that such a reaction may occur in vivo and lead to an inability to repress genes in the liver upon excessive alcohol consumption. This mechanism may play a role in acetaldehyde-induced collagen synthesis in alcoholics.
Acetaldehyde↗
Homology of nuclear factor I with the protein kinase family.
It is observed that a putative DNA binding domain in nuclear factor I (NF I) which is a eukaryotic sequence-specific DNA binding protein participating in both regulation of DNA replication and transcription displays sequence homology with catalytic domains in various protein kinases. In addition, hydropathy analysis reveals that the NF I polypeptide chain is likely to fold into similar secondary and tertiary structures to those of the protein kinases. Although it is not known whether NF I functions as a protein kinase in addition to recognizing a specific sequence on DNA, it is concluded that some of the eukaryotic DNA binding proteins and protein kinases may belong to a gene family, various members of which are evolutionarily related and responsible for the regulation of metabolism in diverse compartments of the cell. The present finding also suggests that a number of kinases may to varying extents be capable of direct interaction with DNA.
Amino Acid Sequence↗