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At least 235 records · Page 13Linked to original sources
PubMed1995

The human replacement histone H3.3B gene (H3F3B).

H3.3 is a replacement histone subtype that is encoded by two replication-independent genes termed H3.3A and H3.3B, respectively. We have isolated a fullsize H3.3 cDNA clone from an oligo(dT)-primed human testicular cDNA library. Subsequently, the corresponding gene was isolated from a human cosmid library and was identified as the H3.3B gene. It was the only histone gene on this 42-kb cosmid clone. The gene structure shows characteristic features of an H3.3 gene. First, it contains an intron of about 0.5 kb in the 5' untranslated region and two smaller introns within the coding gene portion. Second, no histone gene-specific dyad symmetry element was found in the 3' untranslated region, but three putative polyadenylation signals were detected downstream of the gene. The corresponding transcripts were detected by Northern blot analysis using poly(A)+ RNA from testis and from the HEK293 tumor cell line. The newly discovered human H3.3B gene (HGMW-approved symbol H3F3B) was mapped by fluorescence in situ hybridization to the telomeric region of chromosome 17 (17q25). This localization of the H3.3B gene and its solitary arrangement contrast with the majority of the replication-dependent histone genes, which form a large cluster on chromosome 6 and a second cluster on chromosome 1.

Amino Acid Sequence↗
PubMed1997

H3.3A variant histone mRNA containing an alpha-globin insertion: modulated expression during mouse gametogenesis correlates with meiotic onset.

Replacement-variant H3.3 histones have been isolated and sequenced in different eukaryotes, but no functional H3.3A gene has been characterized in the mouse so far. We have cloned an H3.3A cDNA from a mouse fetal ovary library, differentially screened with testis versus somatic cDNA probes. We showed this gene contains a region homologous to the reverse and complementary alpha-globin gene. We believe such a structure could have been generated by retroposition during the evolution of both globin and histone gene families. The sequence coding for H3.3A is 76.6% homologous to the mouse H3.3B gene at the nucleotide level and differs in only one amino acid at the protein level. The high degree of homology between these genes and the H3.3 variant histones from other eukaryotes reveals the conservation of these replication-independent class of histones throughout evolution. Analysis of gene expression reveals a developmental regulation concurrent with meiotic progression, with the highest level of transcript detection coincident with meiotic onset during both oogenesis and spermatogenesis.

Amino Acid Sequence↗
PubMed1985

Replacement variant histone genes contain intervening sequences.

The nucleotide sequences of two chicken histone genes encoding replacement variant H3.3 polypeptides are described. Unlike the replication variant genes of chickens (and almost all other organisms), these genes contain intervening sequences; introns are present in both genes in the 5' noncoding and coding sequences. Furthermore, the replacement variant histone mRNAs are post-transcriptionally polyadenylated. The locations, but not the sizes, of the two introns within the coding segments of the two genes have been exactly conserved, whereas the intron positions in their respective 5' flanking regions differ. Although both H3.3 genes predict the identical histone polypeptide sequence, they are as different from one another as each of them is from a more common replication variant H3.2 gene in silent base substitutions within the coding sequences. Thus, the H3.3 polypeptide sequence has been precisely maintained over a great evolutionary period, suggesting that this class of histones performs a strongly selected biological function. Although replacement variant histones can account for more than 50% of the total H3 protein in the nuclei of specific chicken tissues, the steady-state level of H3.3 mRNA is nearly the same (and is quite low) in all tissues and ages of animals examined. These properties suggest novel mechanisms for the control of the basal histone biosynthesis which takes place outside of the S phase of the cell cycle.

Age Factors↗
PubMed1977

Application of the avidin-biotin method of gene enrichment to the isolation of long double-stranded DNA containing specific gene sequences.

A method of enriching for long double-stranded segments of eukaryotic DNA carrying particular genes is described. A purified RNA coded for by the gene is covalently attached to biotin via the protein, cytochrome c. This modified RNA is hybridized to total nuclear, double-stranded DNA under conditions that allow the formation of R-loops. Avidin, which has a high affinity for biotin, is covalently attached to polymer spheres. The complexes of avidin-spheres with DNA:RNA-biotin R-loop hybrids band in CsCl at a much lower bouyant density than does free DNA. This density is a function of the length of DNA coupled per avidin-sphere. This method was used to prepare very long double-strands of DNA highly enriched in the coding sequences for the large rRNAs of D. melanogaster and L. donovani and the histone mRNAs of S. purpuratus.

Animals↗
PubMed1980

Leader sequences of Strongylocentrotus purpuratus histone mRNAs start at a unique heptanucleotide common to all five histone genes.

We have determined the sequence of the untranslated leader nucleotides of all five histone mRNAs from Strongylocentrotus purpuratus by the dideoxy chain termination method. Total polysomal RNA from sea urchin embryos was used as a substrate for cDNA synthesis primed by specific DNA restriction fragments. Each of the primers was derived from the 5'-terminal part of the coding region for a different histone protein. The five histone mRNA leader sequences are different in length and primary structure. The 5' termini of all five histone mRNAs coincide with the unique heptanucleotide Py-Py-A-T-T-C-Pu in genomic DNA. This sequence, which defines the start of the individual histone mRNAs, is preceded by the A+T-rich octanucleotide identified in front of all eukaryotic structural genes where sequences have been determined to date.

Animals↗
PubMed1998

Histone- and protamine-DNA association: conservation of different patterns within the beta-globin domain in human sperm.

Most DNA in human sperm is bound to highly basic proteins called protamines, but a small proportion is complexed with histones similar to those found in active chromatin. This raises the intriguing possibility that histones in sperm are marking sets of genes that will be preferentially activated during early development. We have examined the chromatin structure of members of the beta-globin gene family, which are expressed at different times in development, and the protamine 2 gene, which is expressed in spermatids prior to the widespread displacement of histones by transition proteins. The genes coding for epsilon and gamma globin, which are active in the embryonic yolk sac, contain regions which are histone associated in the sperm. No histone-associated regions are present at the sites tested within the beta- and delta-globin genes which are silent in the embryonic yolk sac. The trends of histone or protamine association are consistent for samples from the same person, and no significant between-subject variations in these trends are found for 13 of the 15 fragments analyzed in the two donors. The results suggest that sperm chromatin structures are generally similar in different men but that the length of the histone-associated regions can vary. The association of sperm DNA with histones or protamines sometimes changes within as little as 400 bp of DNA, suggesting that there is fine control over the retention of histones.

Binding Sites↗
PubMed1986

Different micrococcal nuclease cleavage patterns characterize transcriptionally active and inactive sea-urchin histone genes.

The micrococcal nuclease cleavage sites have been mapped in the H2A coding and flanking regions of the sea-urchin histone DNA chromatin. A hypersensitive area, centered around - 100 base pairs from the H2A starting site, is found only in embryos actively transcribing the alpha-subtype histone genes. In mesenchyme blastula embryos, upon inactivation of the H2A gene, this region becomes protected while two other areas, near the transcription starting site and in the proximity of the 3' palindromic sequence, become preferential targets for the enzyme. Analysis of the pattern of micrococcal nuclease cleavage on the same region of the histone gene cluster in sperm and late blastula chromatin and on the corresponding segment of protein-free DNA indicates that distinct nucleosomal arrangements characterize the histone genes in the two cell populations.

Animals↗
PubMed1986

An intervening sequence in an unusual histone H1 gene of Tetrahymena thermophila.

An intervening sequence of 254 base pairs interrupts the coding region of the single gene for macronuclear histone H1 of the ciliated protozoan, Tetrahymena thermophila. The intervening sequence has splice junctions similar to those found in RNA polymerase II genes of other organisms. No obvious similarities are observed between this intron and the self-splicing intervening sequence of the Tetrahymena ribosomal gene. The derived amino acid sequence describes a small extremely basic H1 protein missing most of the central hydrophobic domain that is conserved in all other H1 proteins. Macronuclei divide amitotically, without chromosome condensation, suggesting the conserved globular domain of H1 plays a role in higher-order chromatin structure.

Amino Acid Sequence↗
PubMed1988

Complete murine cDNA sequence, genomic structure, and tissue expression of the high mobility group protein HMG-I(Y).

A cDNA coding for the non-histone chromosomal protein HMG-I, or its isoform HMG-Y, was isolated from a murine Friend cell library using synthetic oligonucleotide hybridization probes. Sequence analysis showed that the 1670-base pair full length cDNA insert consists of a 201-base pair, G/C-rich (74%), 5'-untranslated region, a 288-base pair amino acid coding sequence, and an unusually long 1182-base pair 3'-untranslated region. The deduced 96-residue amino acid coding sequence of the murine HMG-I(Y) cDNA is very similar to the reported amino acid sequence of human HMG-I, except that it lacks 11 internal amino acids reported in the human protein. Based on Southern blot hybridization analysis of genomic DNA, there appear to be fewer than five copies of HMG-I(Y) genes in the haploid murine genome. These murine HMG-I(Y) genes contain a large (at least 890 base pairs) exon that includes most, or all, of the 3'-untranslated region; whereas the much shorter 5'-untranslated region and amino acid coding sequences are interrupted by at least one intron. A single size class (approximately 1700 nucleotides in murine cells and 2000 nucleotides in human cells) of HMG-I(Y) mRNAs was detected at high levels in total RNA extracts from rapidly dividing, transformed cells, but to a lesser extent, or not at all, in extracts from slowly or non-dividing cells.

Amino Acid Sequence↗
PubMed1997

Purification of mouse H1 histones expressed in Escherichia coli.

We amplified the coding regions of the previously cloned H1 genes H1-1, H1 zero and H1t and inserted them into the expression vector pET-11d. The synthesis of the H1 histones can be induced in the appropriate strains of bacteria, and the H1 histones can be readily purified. We report detailed protocols for the purification of the expressed proteins using combinations of ion-exchange and reverse-phase HPLC. Sufficient amounts of each pure variant protein can be obtained for use in physical studies of H1-DNA interactions.

Animals↗
PubMed1987

Molecular evolution of the Saccharomyces cerevisiae histone gene loci.

The core histone genes of Saccharomyces cerevisiae are arranged as duplicate nonallelic sets of specifically paired genes. The identity of structural organization between the duplicated gene pairs would have its simplest evolutionary origin in the duplication of a complete locus in a single event. In such a case, the time since the duplication of one of the genes should be identical to that since duplication of the gene adjacent to it on the chromosome. A calculation of the evolutionary distances between the coding DNA sequences of the histone genes leads to a duplication paradox: The extents of sequence divergence in the silent component of third-base positions for adjacent pairs of genes are not identical. Estimates of the evolutionary distance between the two H3-H4 noncoding intergene DNA sequences are large; the divergence between the two separate sequences is indistinguishable from the divergence between either of the regions and a randomly generated permutation of itself. These results suggest that the duplication event may have occurred much earlier than previously estimated. The potential age of the duplication, and the attractive simplicity of the duplication of both the H3-H4 and the H2A-H2B gene pairs having taken place in a single event, leads to the hypothesis that modern haploid S. cerevisiae may have evolved by diploidization or fusion of two ancient fungi.

Base Sequence↗
PubMed1992

Code domains in tandem repetitive DNA sequence structures.

Traditionally, many people doing research in molecular biology attribute coding properties to a given DNA sequence if this sequence contains an open reading frame for translation into a sequence of amino acids. This protein coding capability of DNA was detected about 30 years ago. The underlying genetic code is highly conserved and present in every biological species studied so far. Today, it is obvious that DNA has a much larger coding potential for other important tasks. Apart from coding for specific RNA molecules such as rRNA, snRNA and tRNA molecules, specific structural and sequence patterns of the DNA chain itself express distinct codes for the regulation and expression of its genetic activity. A chromatin code has been defined for phasing of the histone-octamer protein complex in the nucleosome. A translation frame code has been shown to exist that determines correct triplet counting at the ribosome during protein synthesis. A loop code seems to organize the single stranded interaction of the nascent RNA chain with proteins during the splicing process, and a splicing code phases successive 5' and 3' splicing sites. Most of these DNA codes are not exclusively based on the primary DNA sequence itself, but also seem to include specific features of the corresponding higher order structures. Based on the view that these various DNA codes are genetically instructive for specific molecular interactions or processes, important in the nucleus during interphase and during cell division, the coding capability of tandem repetitive DNA sequences has recently been reconsidered.

Animals↗
PubMed1997

Histone H1 expression varies during the Leishmania major life cycle.

The deduced amino acid sequence of Leishmania major sw3 cDNA reveals the presence of characteristic histone H1 amino acid motifs. However, the open reading frame is of an unusually small size for histone H1 (105 amino acids) because it lacks the coding potential for the central hydrophobic globular domain of linker histones present in other eukaryotes. Here, we provide biochemical evidence that the SW3 protein is indeed a L. major nuclear histone H1, and that it is differentially expressed during the life cycle of the parasite. Due to its high lysine content, the SW3 protein can be purified to a high degree from L. major nuclear lysates with 5% perchloric acid, a histone H1 preparative method. Using an anti-SW3 antibody, this protein is detected as a 17 kDa or as a 17/19 kDa doublet in the nuclear subfraction in different L. major strains. The nuclear localization of the SW3 protein is further supported by immunofluorescence studies. During in vitro promastigote growth, both the sw3 cytoplasmic mRNA and its protein progressively accumulate within parasites from early log phase to stationary phase. Within amastigotes, the high level of H1 expression is maintained but decreases when amastigotes differentiate into promastigotes. Together, these observations suggest that the different levels of this histone H1 protein could influence the varying degrees of chromatin condensation during the life-cycle of the parasite, and provide us with tools to study this mechanism.

Amino Acid Sequence↗
PubMed1996

Cell cycle-regulated binding of nuclear proteins to elements within a mouse H3.2 histone gene.

The histone gene family in mammals consists of 15-20 genes for each class of nucleosomal histone protein. These genes are classified as either replication-dependent or -independent in regard to their expression in the cell cycle. The expression of the replication-dependent histone genes increases dramatically as the cell prepares to enter S phase. Using mouse histone genes, we previously identified a coding region activating sequence (CRAS) involved in the upregulation of at least two (H2a and H3) and possibly all nucleosomal replication-dependent histone genes. Mutation of two seven-nucleotide elements, alpha and omega, within the H3 CRAS causes a decrease in expression in stably transfected Chinese hamster ovary cells comparable with the effect seen upon deletion of the entire CRAS. Further, nuclear proteins interact in a highly specific manner with nucleotides within these sequences. Mutation of these elements abolishes DNA/protein interactions in vitro. Here we report that the interactions of nuclear factors with these elements are differentially regulated in the cell cycle and that protein interactions with these elements are dependent on the phosphorylation/dephosphorylation state of the nuclear factors.

Animals↗
PubMed1982

Sea urchin (lytechinus pictus) late-stage histone H3 and H4 genes: characterization and mapping of a clustered but nontandemly linked multigene family.

We have cloned and characterized members of a small multigene family that encodes late-stage histone H3 and H4 mRNAs from the sea urchin Lytechinus pictus. Unlike their highly repetitive histone gene counterparts, which are expressed at an earlier developmental stage, late H3 and H4 histone genes are not present in tandem repeats. In addition, the late stage H3 and H4 genes are not always tightly clustered together with the H1, H2A and H2B genes as they are in early histone genes. The spacer DNA that separates adjoining H3 and H4 coding regions is not conserved between nonallelic members of the late histone gene family. We have determined the nucleotide sequence of a continuous 2100 bp segment of DNA including both H3 and H4 coding sequences, the entire spacer DNA separating the genes and surrounding nonhistone DNA. The late histone H3 and H4 genes encode proteins identical to their early gene counterparts; however, the 5' leader sequence is shorter in late genes and the codon usage is different.

Animals↗
PubMed1978

Sea urchin nuclei use RNA polymerase II to transcribe discrete histone RNAs larger than messengers.

RNA transcribed in isolated sea urchin nuclei and assayed by hybridization to histone genes cloned in E. coli contains sequences homologous to each of the five histone genes. Histone RNA is synthesized exclusively from the same DNA strand which is the template in vivo. Synthesis of the histone gene transcripts is sensitive to alpha-amanitin concentrations which inhibit RNA polymerase II activity. The fraction of histone RNA synthesized in vitro is comparable at two developmental stages to the fraction synthesized in vivo. The nuclear histone transcripts contain sequences homologous to spacer DNA regions present between the coding regions of the 6500 base pair (bp) histone gene repeat unit. The transcription of spacer sequences was demonstrated by hybridization of the nuclear transcripts to subcloned spacer DNA. Although the bulk of the RNA transcripts are greater than 2000 bases long, the histone-specific transcripts are of discrete sizes ranging from 100 bases to about 1100 bases long. Each histone gene hybridizes with at least one of the larger transcripts and with a different subset of smaller RNAs. We do not detect any giant polycistronic transcript spanning the entire histone repeat unit.

Amanitins↗
PubMed1985

Isolation of a mammalian sequence capable of conferring cell cycle regulation to a heterologous gene.

A hybrid gene containing the 5' sequence of a hamster histone H3 gene and the coding sequence of the bacterial neomycin-resistance gene (neo) was constructed. Upon transfection into the hamster fibroblast cell line K12, the hybrid gene exhibited cell cycle-dependent regulation, as evidenced by the maximal accumulation of the neo transcripts during synthesis of DNA in the cell cycle. In addition, cells arrested in the prereplicative phase, as a consequence of the K12 temperature-sensitive mutation, produced significantly less neo messenger RNA.

Animals↗