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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have cloned, mapped and sequenced the complete CDC14 gene of Saccharomyces cerevisiae and characterized its transcription during the cell cycle. CDC14 was found within a 3.5-kilobase pair XhoI-XbaI fragment of chromosome VI. The DNA sequence reveals an open reading frame capable of encoding a 423-amino acid polypeptide. Protein sequence comparisons through the Prosite, GenBank and EMBL databases allowed us to identify a conserved protein tyrosine phosphatase active site in the encoded CDC14 protein beginning at amino acid 153. Disruption demonstrates that CDC14 is an essential gene. The level of the CDC14 transcript appears to be weakly cell cycle-regulated and has a periodicity which lags approximately 15 min behind histone HTB1 mRNA accumulation levels. DNA sequence analysis has identified a region within the CDC14 promoter which bears a striking resemblance (15 out of 21 base pairs identity) to the cell cycle regulation region of the promoter of the histone H2A1-H2B1 (HTA1-HTB1) gene pair. The cell cycle regulation sequence is responsible for the periodic accumulation and hydroxyurea sensitivity of the histone HTA1-HTB1 message. However, unlike histone mRNA, which is repressed upon hydroxyurea arrest, CDC14 mRNA appears to be unaffected. This suggests that CDC14 and histone genes are regulated by different mechanisms during the cell cycle. Furthermore, superhelical density measurements suggest that CDC14 is not involved in nucleosome assembly.
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PMID:CDC14 of Saccharomyces cerevisiae. Cloning, sequence analysis, and transcription during the cell cycle. 159 62

Changes in histone gene dosage as well as mutations within some histone genes suppress delta insertion mutations in the HIS4 and LYS2 loci of Saccharomyces cerevisiae by altering the site of transcription initiation. We have found that three histone regulatory (hir) mutations, identified by their effects on the regulation of histone gene expression, suppress the same insertion mutations. In addition, we have examined whether any previously identified spt (suppressor of Ty) mutations might suppress the delta insertion alleles because of effects on histone gene regulation. Our results demonstrate that mutations in the histone genes SPT11/HTA1 and SPT12/HTB1 and in three other SPT genes, SPT1, SPT10 and SPT21, confer Hir- phenotypes. The spt1 mutation was found to be an allele of HIR2 while the spt10 and spt21 mutations are not in any of the known HIR genes.
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PMID:Histone regulatory (hir) mutations suppress delta insertion alleles in Saccharomyces cerevisiae. 165 65

The two divergently transcribed H2A-H2B gene pairs in yeast are differentially regulated as a function of the copy number of histone genes. Transcription of an HTA2-lacZ reporter gene is independent of histone gene copy number. Transcription of an HTA1-lacZ gene can be repressed or derepressed, depending on the number of HTA plus HTB genes in cells. Regulation by histone gene dosage is dependent on a negative site in the HTA1-HTB1 promoter and the products of regulatory genes that act through this site. The level of H2A plus H2B protein in the cell may signal the response to histone gene copy number, suggesting that transcription of the HTA1-HTB1 locus can be autogenously regulated. This phenomenon may be used, in part, to maintain the balanced synthesis of histones, a critical parameter in nucleosome assembly.
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PMID:A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number. 219 21

Chromatin structure is believed to be important for a number of cellular processes, including transcription. However, the role of nucleosomes in transcription is not well understood. We have identified the yeast histone locus HTB1-HTB1, encoding histones H2A and H2B, as a suppressor of solo delta insertion mutations that inhibit adjacent gene expression. The HTA1-HTB1 locus causes suppression either when present on a high-copy-number plasmid or when mutant. These changes in HTA1-HTB1 after transcription of the genes adjacent to the delta insertions. On the basis of this result, we have examined the effects of increased and decreased histone gene dosage for all four yeast histone loci. From the types of histone gene dosage changes that cause suppression of insertion mutations, we conclude that altered stoichiometry of histone dimer sets can alter transcription in yeast.
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PMID:Changes in histone gene dosage alter transcription in yeast. 283 70

Using a Saccharomyces cerevisiae strain containing an integrated copy of an H2A-lacZ fusion gene, we screened for mutants which overexpressed beta-galactosidase as a way to identify genes which regulate transcription of the histone genes. Five recessive mutants with this phenotype were shown to contain altered regulatory genes because they had lost repression of HTA1 transcription which occurs upon inhibition of chromosome replication (D. E. Lycan, M. A. Osley, and L. Hereford, Mol. Cell. Biol. 7:614-621, 1987). Periodic transcription was affected in the mutants as well, since the HTA1 gene was transcribed during the G1 and G2 phases of the cell cycle, periods in the cell cycle when this gene is normally not expressed. A similar loss of cell cycle-dependent transcription was noted for two of the three remaining histone loci, while the HO and CDC9 genes continued to be expressed periodically. Using isolated promoter elements inserted into a heterologous cycl-lacZ fusion gene, we demonstrated that the mutations fell in genes which acted through a negative site in the TRT1 H2A-H2B promoter.
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PMID:Trans-acting regulatory mutations that alter transcription of Saccharomyces cerevisiae histone genes. 312 20

Nucleosomes have been shown to repress transcription both in vitro and in vivo. However, the mechanisms by which this repression is overcome are only beginning to be understood. Recent evidence suggests that in the yeast Saccharomyces cerevisiae, many transcriptional activators require the SNF/SWI complex to overcome chromatin-mediated repression. We have identified a new class of mutations in the histone H2A-encoding gene HTA1 that causes transcriptional defects at the SNF/SWI-dependent gene SUC2. Some of the mutations are semidominant, and most of the predicted amino acid changes are in or near the N- and C-terminal regions of histone H2A. A deletion that removes the N-terminal tail of histone H2A also caused a decrease in SUC2 transcription. Strains carrying these histone mutations also exhibited defects in activation by LexA-GAL4, a SNF/SWI-dependent activator. However, these H2A mutants are phenotypically distinct from snf/swi mutants. First, not all SNF/SWI-dependent genes showed transcriptional defects in these histone mutants. Second, a suppressor of snf/swi mutations, spt6, did not suppress these histone mutations. Finally, unlike in snf/swi mutants, chromatin structure at the SUC2 promoter in these H2A mutants was in an active conformation. Thus, these H2A mutations seem to interfere with a transcription activation function downstream or independent of the SNF/SWI activity. Therefore, they may identify an additional step that is required to overcome repression by chromatin.
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PMID:A new class of histone H2A mutations in Saccharomyces cerevisiae causes specific transcriptional defects in vivo. 789 95

The Saccharomyces cerevisiae genome contains four loci that encode histone proteins. Two of these loci, HTA1-HTB1 and HTA2-HTB2, each encode histones H2A and H2B. The other two loci, HHT1-HHF1 and HHT2-HHF2, each encode histones H3 and H4. Because of their redundancy, deletion of any one histone locus does not cause lethality. Previous experiments demonstrated that mutations at one histone locus, HTA1-HTB1, do cause lethality when in conjunction with mutations in the SPT10 gene. SPT10 has been shown to be required for normal levels of transcription of several genes in S. cerevisiae. Motivated by this double-mutant lethality, we have now investigated the interactions of mutations in SPT10 and in a functionally related gene, SPT21, with mutations at each of the four histone loci. These experiments have demonstrated that both SPT10 and SPT21 are required for transcription at two particular histone loci, HTA2-HTB2 and HHF2-HHT2, but not at the other two histone loci. These results suggest that under some conditions, S. cerevisiae may control the level of histone proteins by differential expression of its histone genes.
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PMID:SPT10 and SPT21 are required for transcription of particular histone genes in Saccharomyces cerevisiae. 803 1

Both activation and repression have been implicated in the cell cycle-regulated transcription of the histone HTA1-HTB1 locus in Saccharomyces cerevisiae. Transcriptional repressors have been identified through the isolation of recessive mutations in the HIR1, HIR2 and HIR3 genes. These three regulatory genes encode proteins that act at a negative site in the HTA1-HTB1 promoter, and their inactivation results in cell cycle-independent transcription. We report here on the characterization of a fourth HIR mutant. The HIR4-1 mutation is dominant, and the phenotypes that it confers suggest that the mutant gene encodes an altered transcriptional activator. The function of this activator is very specific: it uniquely regulates transcription of the HTA1-HTB1 locus, and it may antagonize repressors that act through the HTA1-HTB1 negative site.
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PMID:The HIR4-1 mutation defines a new class of histone regulatory genes in Saccharomyces cerevisiae. 822 24

The products of the HIR1 and HIR2 genes have been defined genetically as repressors of histone gene transcription in S. cerevisiae. A mutation in either gene affects cell cycle regulation of three of the four histone gene loci; transcription of these loci occurs throughout the cell cycle and is no longer repressed in response to the inhibition of DNA replication. The same mutations also eliminate autogenous regulation of the HTA1-HTB1 locus by histones H2A and H2B. The HIR1 and HIR2 genes have been isolated, and their roles in the transcriptional regulation of the HTA1-HTB1 locus have been characterized. Neither gene encodes an essential protein, and null alleles derepress HTA1-HTB1 transcription. Both HIR genes are expressed constitutively under conditions that lead to repression or derepression of the HTA1 gene, and neither gene regulates the expression of the other. The sequence of the HIR1 gene predicts an 88-kDa protein with three repeats of a motif found in the G beta subunit of retinal transducin and in a yeast transcriptional repressor, Tup1. The sequence of the HIR2 gene predicts a protein of 98 kDa. Both gene products contain nuclear targeting signals, and the Hir2 protein is localized in the nucleus.
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PMID:Characterization of HIR1 and HIR2, two genes required for regulation of histone gene transcription in Saccharomyces cerevisiae. 841 31

Although variants have been identified for every class of histone, their functions remain unknown. We have been studying the histone H2A variant hv1 in the ciliated protozoan Tetrahymena thermophila. Sequence analysis indicates that hv1 belongs to the H2A.F/Z type of histone variants. On the basis of the high degree of evolutionary conservation of this class of histones, they are proposed to have one or more distinct and essential functions that cannot be performed by their major H2A counterparts. Considerable evidence supports the hypothesis that the hv1 protein in T. thermophila and hv1-like proteins in other eukaryotes are associated with active chromatin. In T. thermophila, simple mass transformation and gene replacement techniques have recently become available. In this report, we demonstrate that either the HTA1 gene or the HTA2 gene, encoding the major H2As, can be completely replaced by disrupted genes in the polyploid, transcriptionally active macronucleus, indicating that neither of the two genes is essential. However, only some of the HTA3 genes encoding hv1 can be replaced by disrupted genes, indicating that the H2A.F/Z type variants have an essential function that cannot be performed by the major H2A genes. Thus, an essential gene in T. thermophila can be defined by the fact that it can be partially, but not completely, eliminated from the polyploid macronucleus. To our knowledge, this study represents the first use of gene disruption technology to study core histone gene function in any organism other than yeast and the first demonstration of an essential gene in T. thermophila using these methods. When a rescuing plasmid carrying a wild-type HTA3 gene was introduced into the T. thermophila cells, the endogenous chromosomal HTA3 could be completely replaced, defining a gene replacement strategy that can be used to analyze the function of essential genes.
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PMID:Essential and nonessential histone H2A variants in Tetrahymena thermophila. 875 31


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