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PubMed1988

Drosophila has a single copy of the gene encoding a highly conserved histone H2A variant of the H2A.F/Z type.

The Tetrahymena histone H2A variant designated hv1 is localized exclusively in the transcriptionally active macronucleus and is absent from the quiescent micronucleus (1). A cDNA clone of the hv1 gene (2) was used to screen a Drosophila cDNA library. A cross-hybridizing clone was recovered and shown by sequence analysis to code for a protein homologous to hv1 as well as to the chicken H2A variant, H2A.F (3), the sea urchin H2A variant, H2A.F/Z (4) and the mammalian H2A variant H2A.Z (5). Southern analysis of Drosophila genomic DNA indicates that the H2AvD (H2A variant Drosophila) gene is present in one copy. In situ hybridization places the locus at 97CD on chromosome 3, while the S-phase regulated histone genes are on chromosome 2 (6). Thus the Drosophila H2A variant should be accessible to genetic analysis, which will enable its function to be determined.

Amino Acid Sequence↗
PubMed2002

Identification and characterization of the genes encoding the core histones and histone variants of Neurospora crassa.

We have identified and characterized the complete complement of genes encoding the core histones of Neurospora crassa. In addition to the previously identified pair of genes that encode histones H3 and H4 (hH3 and hH4-1), we identified a second histone H4 gene (hH4-2), a divergently transcribed pair of genes that encode H2A and H2B (hH2A and hH2B), a homolog of the F/Z family of H2A variants (hH2Az), a homolog of the H3 variant CSE4 from Saccharomyces cerevisiae (hH3v), and a highly diverged H4 variant (hH4v) not described in other species. The hH4-1 and hH4-2 genes, which are 96% identical in their coding regions and encode identical proteins, were inactivated independently. Strains with inactivating mutations in either gene were phenotypically wild type, in terms of growth rates and fertility, but the double mutants were inviable. As expected, we were unable to isolate null alleles of hH2A, hH2B, or hH3. The genomic arrangement of the histone and histone variant genes was determined. hH2Az and the hH3-hH4-1 gene pair are on LG IIR, with hH2Az centromere-proximal to hH3-hH4-1 and hH3 centromere-proximal to hH4-1. hH3v and hH4-2 are on LG IIIR with hH3v centromere-proximal to hH4-2. hH4v is on LG IVR and the hH2A-hH2B pair is located immediately right of the LG VII centromere, with hH2A centromere-proximal to hH2B. Except for the centromere-distal gene in the pairs, all of the histone genes are transcribed toward the centromere. Phylogenetic analysis of the N. crassa histone genes places them in the Euascomycota lineage. In contrast to the general case in eukaryotes, histone genes in euascomycetes are few in number and contain introns. This may be a reflection of the evolution of the RIP (repeat-induced point mutation) and MIP (methylation induced premeiotically) processes that detect sizable duplications and silence associated genes.

Amino Acid Sequence↗
PubMed1991

Structural organization and transcription of plant mitochondrial and chloroplast genomes.

Experimental evidence is presented showing that the plant mitochondrial and chloroplast genomes are multipartite and, that besides a large circular genomic DNA, they contain subgenomic minicircular and plasmid-like molecules. It is demonstrated that plant mitochondrial and chloroplast DNAs are packaged into deoxynucleoprotein fibrils comprising nucleosome-like and nucleomere-like globules; the fibrils form loops and rosette-like structures with central proteinaceous components. A similar structure is characteristic of the subgenomic DNAs. The basic proteins involved in the formation of nucleosome-like globules are quite different from the nuclear histones, indeed the basic proteins from plant mitochondria and chloroplasts are also distinct. Some of the basic proteins share common antigens with the E. coli HU protein. The genetic code for the mitochondrial and chloroplast genes is universal. The only codon now thought to be different from the universal in the mitochondrial genome is corrected during post-transcriptional mRNA editing. There are two hexanucleotides in the promoters of the chloroplast genes homologous to the sequences in -10 and -35 regions of the prokaryotic genes promoters requisite for transcription. Promoter sequences of the plant mitochondria genes responsible for transcription regulation were not identified. Immunoelectronmicroscopic evidence suggest that mitochondrial and chloroplast RNA polymerases have antigens in common with the beta-subunit of E. coli RNA polymerase. It is shown that the mitochondrial genes are intensely transcribed in the dark and repressed by illumination. Electron microscopy demonstrated that about 70% of plant mitochondria contain numerous RNA polymerase molecules in the dark, but this percentage falls to 10-15% after light exposure.

Chloroplasts↗
PubMed2006

Birth of a chimeric primate gene by capture of the transposase gene from a mobile element.

The emergence of new genes and functions is of central importance to the evolution of species. The contribution of various types of duplications to genetic innovation has been extensively investigated. Less understood is the creation of new genes by recycling of coding material from selfish mobile genetic elements. To investigate this process, we reconstructed the evolutionary history of SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element. We show that the transposase gene was recruited as part of SETMAR 40-58 million years ago, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously noncoding sequence and the creation of a new intron. The original structure of the fusion gene is conserved in all anthropoid lineages, but only the N-terminal half of the transposase is evolving under strong purifying selection. In vitro assays show that this region contains a DNA-binding domain that has preserved its ancestral binding specificity for a 19-bp motif located within the terminal-inverted repeats of Hsmar1 transposons and their derivatives. The presence of these transposons in the human genome constitutes a potential reservoir of approximately 1,500 perfect or nearly perfect SETMAR-binding sites. Our results not only provide insight into the conditions required for a successful gene fusion, but they also suggest a mechanism by which the circuitry underlying complex regulatory networks may be rapidly established.

Amino Acid Sequence↗
PubMed2005

Independent regulation of H-NS-mediated silencing of the bgl operon at two levels: upstream by BglJ and LeuO and downstream by DnaKJ.

Silencing of the Escherichia coli bgl operon by the histone-like nucleoid-structuring protein H-NS occurs at two levels. Binding of H-NS upstream of the promoter represses transcription initiation, whilst binding within the coding region is also proposed to repress transcription elongation. The latter, downstream level of repression is counteracted by the protease Lon and, thus, silencing of the bgl operon is more effective in lon mutants. Transposon-mutagenesis screens for suppression of this lon phenotype on bgl were performed and insertion mutations disrupting rpoS and crl were obtained, as well as mutations mapping upstream of the open reading frames of bglJ, leuO and dnaK. In rpoS and crl mutants, bgl promoter activity is known to be higher. Likewise, as shown here, bgl promoter activity is increased in the bglJ and leuO mutants, which express BglJ and LeuO constitutively. However, BglJ and LeuO have no impact on downstream repression. A dnaKJ mutant was isolated for the first time in the context of the bgl operon. The mutant expresses lower levels of DnaK than the wild-type. Interestingly, in this dnaKJ : : miniTn10 mutant, downstream repression of bgl by H-NS is less effective, whilst upstream repression by H-NS remains unaffected. Together, the data show that the two levels of bgl silencing by H-NS are regulated independently.

Bacterial Proteins↗
PubMed2006

Evidence that Spt2/Sin1, an HMG-like factor, plays roles in transcription elongation, chromatin structure, and genome stability in Saccharomyces cerevisiae.

Spt2/Sin1 is a DNA binding protein with HMG-like domains that has been suggested to play a role in chromatin-mediated transcription in Saccharomyces cerevisiae. Previous studies have suggested models in which Spt2 plays an inhibitory role in the initiation of transcription of certain genes. In this work, we have taken several approaches to study Spt2 in greater detail. Our results have identified previously unknown genetic interactions between spt2Delta and mutations in genes encoding transcription elongation factors, including members of the PAF and HIR/HPC complexes. In addition, genome-wide and gene-specific chromatin immunoprecipitation analyses suggest that Spt2 is primarily associated with coding regions in a transcription-dependent fashion. Furthermore, our results show that Spt2, like other elongation factors, is required for the repression of transcription from a cryptic promoter within a coding region and that Spt2 is also required for repression of recombination within transcribed regions. Finally, we provide evidence that Spt2 plays a role in regulating the levels of histone H3 over transcribed regions. Taken together, our results suggest a direct link for Spt2 with transcription elongation, chromatin dynamics, and genome stability.

Chromatin↗
PubMed1981

Isolation of two clusters of mouse histone genes.

Histone mRNA was partially purified from mouse myeloma cells synchronized in S phase by isoleucine starvation. A cDNA was prepared that contained sequences complementary to all five mouse histone genes. This cDNA was used to screen a library of mouse DNA in lambda phage. The positive clones were screened by hybridization with sea urchin histone gene-specific probes to identify those clones that contained histone genes. Confirmation of this identification was obtained by hybridization with Drosophila histone genes. Two independent clusters of histone genes were isolated. One, MM531, contains regions hybridizing specifically to H3, H4, and H1 and the other, MM221, contains two regions hybridizing specifically to H3 and single regions complementary to H4, H2b, and H2a. They are not part of a simple repeating structure. The nucleotide sequence of the coding region of the H3 gene in MM531 has been determined. This gene could code for a variant H3 protein that has several amino acid substitutions not reported in other H3 proteins.

Animals↗
PubMed1976

The occurrence in amino acid sequences of extensive informational symmetries based on possible codon-codon complementarity in the encoding polynucleotides.

1. A procedure is described for the detection and assessment of informational complementarity in an amino acid sequence; it is based on possible autocomplementarity in the mRNA, and involves codon-to-codon matching. 2. This procedure was applied to myelin basic protein, a variety of protamines, histone IV, silk fibroin, rat skin collagen alpha1 chain and a sheep keratin. A multiplicity of extensive low-probability informational symmetries, based on codon-to-codon matching, were detected. 3. These low-probability orderings, which are independent of the actual mRNA codons, are rationalized in terms of the evolutionary ordering of the amino acid sequences concerned, in such a way that constraints on the secondary structure of the coding polynucleotides were satisfied. This possible interpretation is supported by a number of significant common properties of the protein sequences analysed.

Amino Acid Sequence↗
PubMed1982

H3 and H4 histone cDNA sequences from Xenopus: a sequence comparison of H4 genes.

Ovarian poly (A) + RNA from Xenopus laevis and Xenopus borealis was used to construct two cDNA libraries which were screened for histone sequences. cDNA clones to H4 mRNA were obtained from both species and an H3 cDNA clone from Xenopus laevis. The complete DNA sequences of these clones have been determined and are presented. These new sequences are compared with other H3 and H4 DNA sequences both in the coding and 3' noncoding regions. We find that there is considerable non-random codon usage in ten H4 genes. In addition there are some sequence similarities in the 3' noncoding regions of H3 and H4 genes.

Animals↗
PubMed2025

Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time.

The flexibility of the spatio-temporal genome replication program during development and disease highlights the regulatory role of plastic epigenetic mechanisms over genetic determinants. Histone post-translational modifications are broadly implicated in replication timing control, yet the specific mechanisms through which individual histone marks influence replication dynamics, particularly in heterochromatin, remain unclear. Here, we demonstrate that H3K36me3 dynamically enriches at pericentromeric heterochromatin, composed of major satellite DNA repeats, prior to replication during mid S phase in mouse embryonic stem cells. By knocking down lysine 36-specific methyltransferases or by targeting the H3K36M oncohistone to pericentromeric heterochromatin, we reduce global or local H3K36me3 levels, respectively, revealing its essential role in preserving the replication timing of constitutive heterochromatin. Loss of H3K36me3 accompanies increased RNA polymerase II serine-5 phosphorylation and lowered major satellite RNA levels, indicating transcriptional dysregulation. Notably, we identify a strand-specific contribution of major satellite forward transcripts in regulating the replication timing of constitutive heterochromatin and maintaining chromatin stability, highlighting the importance of non-coding RNAs as critical regulators of replication timing.

Heterochromatin↗
PubMed1985

Primary structure of the hip gene of Escherichia coli and of its product, the beta subunit of integration host factor.

We describe the isolation and sequencing of the hip gene of Escherichia coli and show that it encodes the beta subunit of integration host factor (IHF beta). In order to locate the coding region, we constructed a set of deletion mutants by exonucleolytic digestion of a fragment containing hip, determined which mutants were hip+ and which hip- by complementation, and then sequenced the ends of the critical deletions. The 5' end of the coding region was located precisely by comparing the deduced amino acid sequence to the actual N-terminal amino acid sequence of IHF. Our assignment of the coding region was further substantiated by the nucleotide sequences of a hip point mutant and of internal replacement mutations. We found a probable promoter for hip located about 85 base-pairs upstream from the initial AUG codon and about 75 base-pairs downstream from the 3' end of the neighboring gene, rpsA, and we constructed an IHF beta overproducer by fusing the coding sequences to the lambda pL promoter. A survey of known protein sequences revealed a close relationship between IHF beta and the type II prokaryotic DNA binding proteins (the "histone-like" proteins). This relationship is shared to a considerable extent by the other subunit of IHF, IHF alpha. A hip missense mutation that replaces a completely conserved glycine with aspartate has a null phenotype, suggesting that the conserved regions are functionally important.

Amino Acid Sequence↗
PubMed2001

Sequence and analysis of the murine Hmgiy (Hmga1) gene locus.

The HMGIY non-histone proteins play important roles as architectural transcription factors that regulate gene transcription in mammalian cells and also act as host-supplied cofactors necessary for retroviral integration. The genes coding for the HMGIY proteins are proto-oncogenes, and their aberrant or over-expression is correlated with both neoplastic transformation and metastatic progression in a wide variety of tumors. Here, we report the first complete sequence of the murine Hmgiy (a.k.a. Hmga1) gene and provide a detailed comparison of this with the sequence and organization of the human HMGIY gene, including an analysis of its promoter region with the previously unreported 5' upstream region of the human gene. These analyses reveal a remarkable degree of overall sequence conservation in both the protein coding and promoter regions of the murine and human genes, including conservation of the c-Myc binding site that has been demonstrated to regulate murine Hmgiy transcription (Wood et al., 2000. Mol. Cell. Biol. 20, 5490-5502). The promoters of both genes contain other conserved transcription factor binding sites that may also represent important cis-regulatory elements. Two exons present in the 5' untranslated region of the human gene, however, are missing from the murine gene, suggesting that these two closely related mammalian species regulate transcription of their Hmgiy genes in an individualistic manner.

Animals↗
PubMed2001

Code of silence.

Explore the source record for details and available documents.

Chromatin↗
PubMed1981

Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae.

Hybrid genes between the Escherichia coli lacZ gene and the iso-1-cytochrome c (CYC1) gene of Saccharomyces cerevisiae were constructed by recombination in vitro. Each of the hybrid genes encodes a chimeric protein with a cytochrome c moiety at the amino terminus and an active beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) moiety at the carboxy terminus. When these hybrids are introduced into S. cerevisiae on plasmid vectors, they direct synthesis of beta-galactosidase. beta-Galactosidase levels directed by one such plasmid display the pattern of regulation normally seen for cytochrome c (i.e., a reduction of synthesis in cells grown in glucose). This plasmid contains one codon of CYC1 fused to lacZ, and the fused gene is preceded by the 1100 nucleotides that lie upstream from CYC1. An analysis of deletions in the upstream DNA suggests that sequences required for efficient transcription initiation of CYC1 lie within the DNA segment 250--700 base pairs upstream from the start of the CYC1 coding sequence. This region is at least 130 base pairs upstream from the "Hogness box" sequence that precedes the CYC1 coding sequence.

Animals↗
PubMed2002

Isolation of transcriptionally active chromatin from human breast cancer cells using Sulfolink coupling gel chromatography.

The process of transcription unfolds the nucleosome. The unfolded nucleosome structure will be maintained as long as the histones are in a highly acetylated state. Typically the cysteine residue at position 110 of histone H3 is buried in the interior of the nucleosome. However, the transcribed unfolded nucleosome has its H3 cysteine exposed, offering a tag to isolate and study transcribed nucleosomes. In this study, we applied Sulfolink Coupling Gel chromatography to isolate unfolded nucleosomes from estrogen dependent human cancer T5 cells. Inhibition of histone deacetylase activity did not enhance the yield of unfolded nucleosomes from these cells. We show that the estrogen receptor and c-myc transcribed DNA sequences are associated with unfolded nucleosomes. In chromatin immunoprecipitation (ChIPs) assays, we found that the coding regions of the estrogen receptor and c-myc genes are bound to highly acetylated H3 and H4 in cultured T5 Cells. We conclude that in cultured T5 breast cancer cells H3 and H4 are in highly acetylated states maintaining the unfolded structure of the transcribed nucleosome and facilitating subsequent rounds of elongation.

Acetylation↗
PubMed1976

DNA-histones, a computer model.

The model of DNA-histones has the following elements: 1. The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the electrons pi of one nucleotide base are excited, an exchange of protons is produced between the two complementary bases. The result is the displacement of the conjugated double bonds which facilitates the inter-molecular transmission of the electronic wave of excitation by electro-magnetic coupling. 2. Each triplet of nucleotide bases of DNA fixes one definite amino acid (as in the genetic code). Between the nucleotide bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation. 3. An input signal molecule arrives at the receiver gene and unleashes the activity of the enzymes which introduce in the DNA-histones system the electronic wave of excitation. The electronic wave of excitation arises as a result of the break of the high-energy bonds of ATP. Then, the electronic excitation is transmitted to the productor gene where it represents the signal for starting the synthesis of the mRNA.

Adenosine Triphosphate↗
PubMed2005

Global and Hox-specific roles for the MLL1 methyltransferase.

The mixed-lineage leukemia (MLL1/ALL-1/HRX) histone methyltransferase is involved in the epigenetic maintenance of transcriptional memory and the pathogenesis of human leukemias. To understand its role in cell type specification, we determined the human genomic binding sites of MLL1. We found that MLL1 functions as a human equivalent of yeast Set1. Like Set1, MLL1 localizes with RNA polymerase II (Pol II) to the 5' end of actively transcribed genes, where histone H3 lysine 4 trimethylation occurs. Consistent with this global role in transcription, MLL1 also localizes to microRNA (miRNA) loci that are involved in leukemia and hematopoiesis. In contrast to the 5' proximal binding behavior at most protein-coding genes, MLL1 occupies an extensive domain within a transcriptionally active region of the HoxA cluster. The ability of MLL1 to serve as a start site-specific global transcriptional regulator and to participate in larger chromatin domains at the Hox genes reveals dual roles for MLL1 in maintenance of cellular identity.

Chromatin Immunoprecipitation↗
PubMed1986

Genomic organization and nucleotide sequences of two corn histone H4 genes.

The sea urchin histone H4 gene has been used as a probe to clone two corn histone H4 genes from a lambda gtWES X lambda B corn genomic library. The nucleotide (nt) sequences of both genes showed that the encoded amino acid sequences were identical to that of the H4 of pea and one variant of wheat. The nt sequences of the coding regions showed 92% homology. 5'- and 3'-flanking regions do not show extensive nt sequence analogies. Southern blotting of the EcoRI digested genomic DNA suggests the existence of multiple H4 genes dispersed throughout the genome.

Amino Acid Sequence↗