Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10412 (H1.4)
 75 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of doxorubicin (DX) treatment on H1 synthesis and acetylation was studied in two human colon adenocarcinoma cell lines, sensitive (LoVo) and resistant (LoVo/DX) to this drug. Histone variants were resolved by a high resolution two-dimensional gel electrophoresis system coupled to fluorography for the detection of radioactive incorporation. The relative synthesis of H1.4 and H1.5 variants was slightly reduced by DX. This is probably related to the inhibition of DNA synthesis consequent to drug treatment. The main effect is that DX induces the acetylation of H1 isoproteins in the LoVo/DX resistant line but not in the parental line, which is 30 times more sensitive to anthracyclines. The different behavior of the two cell lines cannot be attributed to different cellular drug retention since the DX doses chosen (1.25 for LoVo and 40 micrograms/ml for LoVo/DX cells) correspond to similar intracellular drug concentrations. H1 acetylation persisted after exposure to cycloheximide in DX treated LoVo/DX cells, indicating that it is a postranslational event. The induction of H1 acetylation appears rather specific since no increase was found in 3H-acetate incorporation on the total cellular TCA-precipitable fraction. In addition DX treatment did not modify the acetylation of core histones in either LoVo or LoVo/DX cell lines.
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PMID:Doxorubicin induces the acetylation of histone H1 in a human colon cancer cell line (LoVo/DX) selected for resistance to the drug, but not in the sensitive parental line (LoVo). 317 5

Histones are the major protein constituents of the chromatin of eukaryotic cell nuclei. This group of basic proteins is extremely conserved throughout evolution and includes five classes termed H1, H2A, H2B, H3 and H4. In mammals, each of these classes except H4 is subdivided into several subtypes. The most divergent class of histones is the H1 protein family, which consists of seven different subtypes, termed H1.1-H1.5, H1 degree, and H1t. The subtypes H1.2 and H1.4 are found in most somatic cell nuclei, whereas H1 degree is found in several differentiated tissues, and H1t is restricted to mammalian testicular cells. Similarly, core histone subtypes replacing the major forms of H2A, H2B or H3 have been described. Biochemical analysis of protein and RNA from different tissues and cell lines demonstrates varied patterns of expression of individual histone subtype genes. Moreover, antibodies against specific histone subtypes and in situ hybridization with subtype-specific probes indicate that the expression of histone subtype genes is in several cases modulated in a tissue-specific manner. This is particularly evident at the different stages of spermatogenesis when chromatin undergoes substantial reorganization, which finally results in the highly condensed state of chromatin of the mature sperm head.
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PMID:Histones: genetic diversity and tissue-specific gene expression. 904 36

We have previously located the genes of the five human main type H1 genes and the gene encoding the testicular subtype H1t to the region 21.1 to 22.2 on the short arm of chromosome 6. To investigate the organization of the histone genes in this region, we isolated two YACs from a human YAC library by PCR screening with primers specific for histone H1.1. This screen revealed two YAC clones, YAC Y23 (corresponding to ICRFy901D1223) contains an insert of about 480 kb, whereas the smaller YAC 4A (corresponding to ICRFy900C104) spans about 340 kb and is completely covered by YAC Y23. We have subcloned the YAC inserts in cosmids, determined the linear orientation of the cosmids by cosmid walking, and constructed a restriction map of the entire region by mapping the individual cosmids using partial digests and hybridization with labeled oligonucleotides complementary to the cos site of the vector. Hybridization analysis, subcloning, restriction mapping, and sequencing revealed that most of the previously isolated phage and cosmid clones containing histone genes are part of this YAC including the clones containing the four human main type H1 histone genes H1.1 to H1.4, the H1t gene, and core histone genes. Thirty-five histone genes map within 260 kb of the YAC Y23 insert. All newly identified histone genes were sequenced, and the sequences were deposited with the EMBL nucleotide sequence database. The histone H1.5 gene is not part of this region, and we therefore conclude that the H1.5 gene and the associated core histone genes form a separate subcluster within this chromosomal region.
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PMID:Human histone gene organization: nonregular arrangement within a large cluster. 911 99

Proteolysis of histones H1b and H1(0) is observed after the incubation of rat spleen nuclei at 37 degrees C during 1 hour. Adenosine triphosphate, inorganic pyrophosphate and nicotinamide adenine dinucleotide decrease the digestion of histone H1b. ATP, PP1 and NAD+, in the case of 3 hours incubation, do not affect proteolysis of H1 histones in rat spleen nuclei. The incubation of rat liver nuclei at 37 degrees C during 1 hour leads to a decrease of the amount of histone H1b and, to much more extent, H1a. In this case ATP, PP1 and NAD+ increase proteolysis of histone H1a but practically do not affect proteolysis of H1b. After 2-hours incubations histone H1a is completely digested but histone H1b is partially preserved: ATP in this case, as well as in spleen nuclei, decreases proteolysis of histone H1b. During the 3 hours incubation, when histones H H1a and H1b are completely digested, partial digestion of histone H3 being observed, ATP does not prevent from proteolysis of histone H1b. A protein appears between the H2A and H4 histones after heating at 37 degrees C in both spleen and liver rat nuclei. Neither ATP nor PP1 and NAD+ affect the amount of this protein. It is suggested that the location of histones H1a and H1b in different chromatin domains determines the digestion of these histones by ATP-dependent proteinases.
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PMID:[Effect of adenosine triphosphate on the cleavage of H1 histones in nuclei of rat spleen and liver]. 927 39

Five main type H1 histones have been described in man (H1.1-H1.5) in addition to the testis specific type H1t and the replacement subtype H1 degrees, which is found mainly in highly differentiated cells. We have isolated this whole complement of H1 genes and have studied the expression of the seven human H1 subtype genes in several cell lines. The RNAase protection assay was used to discriminate between the very similar transcripts derived from the seven H1 subtype genes. With the exception of H1.2 and H1.4, we found substantial differences between the H1 mRNA levels in the different cell lines tested. No H1.1 mRNA was detected in most of the cell lines and just a low level of H1.1 mRNA was found in human testis. In contrast to the differential patterns of the other subtypes, H1.2 and H1.4 were in all cells expressed at a high level, indicating a basal function compared with the other H1 histones. Because differences in the timing of H1 protein subtype synthesis have been reported, we have analyzed the kinetics of accumulation of H1 subtypes in synchronized HeLa cells and observed that all H1 subtypes examined (H1 degrees, H1.2-H1.5) were expressed in a replication-dependent manner. The analysis showed a differential rise of mRNA levels during S-phase, from four-fold (H1 degrees) to 15-fold (H1.5). Our results may point at a specific function of each subtype and suggest that expression of the H1 histone subtype genes depends on common S-phase-depent factors as well as on individual regulatory systems. Thus, the data presented here provide a basis for further analysis of the regulation and function of the complex H1 gene and protein family.
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PMID:Varied expression patterns of human H1 histone genes in different cell lines. 932 6

Murine genes encoding the seven H1 histone isoforms H1.1-H1.5, H1(o) and H1t have been isolated and sequenced. We have established expression patterns of these genes in several tissues during postnatal development. For that analysis, RNase protection assay rather than Northern blot hybridization was used, since the sequences of these genes are highly similar and would cross-hybridize under Northern blot conditions. Expression patterns of H1.1 to H1.5 and H1(o) were determined in tissues of animals at days 5, 9 and 20 after birth and of adult mice. In addition, RNA was analyzed in three mouse cell lines (NIH3T3, P19, TM4). Transcription of the subtype genes H1.2 and H1.4 was found in all tissues and cell lines studied. The most varied expression patterns were obtained with the H1.1 subtype. H1.1 mRNA was found at high concentrations in thymus and spleen throughout development and in testis beginning with a low expression in 5-day-old animals and increasing levels in testis RNA from 9- and 20-day-old and adult mice. H1(o) mRNA was found primarily in highly differentiated tissues with concentrations decreasing from 5-day-old to adult animals.
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PMID:Expression of murine H1 histone genes during postnatal development. 965 12

Characteristic steps in the course of cellular apoptosis are the induction of chromatin condensation and cleavage of the DNA, leading to the formation of oligomers of nucleosomes. Since the H1 histones represent functional elements that are essential for the generation of highly condensed chromatin structures, we analysed the total cellular H1 histones of five leukaemic and three solid human tumour cell lines, comparing the H1 pattern of exponentially growing cells with that of apoptotic cells. For the induction of apoptosis, cell lines were treated with the water-soluble camptothecin derivative, topotecan (a topoisomerase I inhibitor), or with an apoptosis-inducing monoclonal anti-CD95 (Fas/APO-1) antibody. Total histone H1 proteins were isolated by extraction with 5% perchloric acid and were analysed by means of capillary zone electrophoresis (CZE) separation. The identities of the peaks representing different histone H1 subtypes on CZE electropherograms were confirmed by analysis of preparations (recombinant proteins purified from transformed yeast used as internal standards) mixed with each of the subtypes respectively. The progress of topotecan- or anti-CD95-induced cell death was monitored by flow cytometry analysis and also by agarose electrophoresis of fragmented DNA. During early apoptosis of three of these cell lines, we observed the induction of internucleosomal DNA cleavage and, simultaneously, a typical change in the histone H1 protein pattern, leading to an increase in the relative amounts of histone subtypes H1.4 and H1.5. Upon apoptosis induction, these changes were only observed in correlation with the occurrence of DNA fragmentation, thus possibly reflecting a prerequisite for DNA accessibility and/or endonuclease activity.
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PMID:Changes in the protein pattern of H1 histones associated with apoptotic DNA fragmentation. 988 31

We have previously shown a connection between histone H1 phosphorylation and the transcriptional competence of the hormone inducible mouse mammary tumor virus (MMTV) promoter. Prolonged exposure of mouse cells to dexamethasone concurrently dephosphorylated histone H1 and rendered the MMTV promoter refractory to hormonal stimulation and, therefore, transcriptionally unresponsive. Using electrospray mass spectrometry, we demonstrate here that prolonged dexamethasone treatment differentially effects a subset of the six somatic H1 isoforms in mouse cells. H1 isoforms H1.0, H1.1, and H1.2 are non-responsive to hormone whereas prolonged dexamethasone treatment effectively dephosphorylated the H1.3, H1.4, and H1.5 isoforms. The protein kinase inhibitor staurosporine, shown to dephosphorylate histone H1 and down-regulate MMTV in cultured cells, appears only to completely dephosphorylate the H1.3 isoform. These results suggest that dephosphorylation of specific histone H1 isoforms may contribute to the previously observed decrease in transcriptional competence of the MMTV promoter through the modulation of chromatin structure. In a broader sense, this work advances the hypothesis that post-translational modifications of individual histone H1 isoforms directly influence the transcriptional activation/repression of specific genes.
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PMID:Hormone-mediated dephosphorylation of specific histone H1 isoforms. 1147 99

Histone post-translational modifications have been implicated in a variety of biological processes such as gene expression, DNA replication, and chromatin assembly. The modifications include methylation, acetylation, phosphorylation, ubiquitination, glycosylation, and ADP-ribosylation. For several years, we have been investigating the role of histone H1 phosphorylation in transcription using the hormone inducible mouse mammary tumor virus (MMTV) promoter. When mouse cells were exposed to prolonged treatment with dexamethasone, a significant decrease in the level of histone H1 phosphorylation was observed. Traditionally, Western analyses with anti-histone H1 and phospho-specific H1 antibodies were performed to observe changes in phosphorylation levels of the bulk H1 histones. More recently, we have applied electrospray ionization mass spectrometry to the analysis of histone H1 isoforms. Utilizing this approach, we have investigated the phosphorylation state of the specific H1 isoforms before and after prolonged treatment with dexamethasone. Specifically, we could determine that the relative phosphorylation levels of the histone H1.3, H1.4, and H1.5 isoforms decrease after prolonged hormone exposure. Recent advancements in mass spectrometry have proven invaluable toward the analysis of post-translational modifications on proteins. The continued developments in the area of mass spectrometry should provide new insights into not only the function of proteins but also into the basic regulatory mechanisms that control cellular functions.
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PMID:Understanding global changes in histone H1 phosphorylation using mass spectrometry. 1503 87

Histone H1 isoforms isolated from asynchronously grown HeLa cells were subjected to enzymatic digestion and analyzed by nano-flow reversed-phase high performance liquid chromatography (RP-HPLC) tandem mass spectrometry (MS/MS) on both quadrupole ion trap and linear quadrupole ion trap-Fourier transform ion cyclotron resonance mass spectrometers. We have observed all five major isoforms of histone H1 (H1.1, H1.2, H1.3, H1.4, and H1.5) as well as a lesser studied H1, isoform H1.X. MS/MS experiments confirmed N-terminal acetylation on all isoforms plus a single internal acetylation site. Immobilized metal affinity chromatography in combination with tandem mass spectrometry was utilized to identify 19 phosphorylation sites on the five major H1 isoforms plus H1.X. Fourteen of these phosphorylation sites were located on peptides containing the cyclin dependent kinase (CDK) consensus motif (S/T)-P-X-Z (where X is any amino acid and Z is a basic amino acid). Five phosphorylation sites were identified in regions that did not fit the consensus CDK motif. One of these phosphorylation sites was found on the serine residue on the H1.4 peptide KARKSAGAAKR. The adjacent lysine residue to the phosphoserine was also shown to be methylated. This finding raises the question of whether the hypothesized "methyl/phos" switch could be extended to linker histones, and not exclusive to core histones.
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PMID:Characterization of phosphorylation sites on histone H1 isoforms by tandem mass spectrometry. 1559 31


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