Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence indicates that transcriptionally silent chromatin structure is dynamic and may change its conformation in response to external or internal stimuli. We show that growth temperature affects all three forms of transcriptional silencing in Saccharomyces cerevisiae. In general, increasing the temperature within the range of 23-37 degrees C strengthens HM and telomeric silencing but reduces rDNA silencing. High temperature (37 degrees C) can suppress the silencing defects of histone H4 mutants. We demonstrate that DNA at the silent HML locus becomes more and more negatively supercoiled as temperature increases in a Sir-dependent manner, which is indicative of enhanced silent chromatin. This enhancement of silent chromatin is not dependent on silencers and therefore does not require de novo assembly of silent chromatin. We also present evidence suggesting that MAP kinase-mediated Sir3p hyperphosphorylation, which plays a role in regulating silencing in response to certain stress conditions, is not involved in high temperature-induced strengthening of silencing. In addition, Pnc1p, a positive regulator of Sir2p activity, plays no role in thermal regulation of silencing. Therefore, growth temperature regulates transcriptional silencing by a novel mechanism.
J Mol Biol 2004 Dec 03
PMID:Regulation of transcriptional silencing in yeast by growth temperature. 1554

Human endogenous retroviruses (HERVs) are the remnants of ancient germ cell infection by exogenous retroviruses and occupy up to 8% of the human genome. It has been suggested that HERV sequences have contributed to primate evolution by regulating the expression of cellular genes and mediating chromosome rearrangements. After integration approximately 28 million years ago, members of the HERV-K (HML-2) family have continued to amplify and recombine. To investigate the utility of HML-2 polymorphisms as markers for the study of more recent human evolution, we compiled a list of the structure and integration sites of sequences that are unique to humans and screened each insertion for polymorphism within the human genome databases. Of the total of 74 HML-2 sequences, 18 corresponded to complete or near-complete proviruses, 49 were solitary long terminal repeats (LTRs), 6 were incomplete LTRs, and 1 was a SVA retrotransposon. A number of different allelic configurations were identified including the alternation of a provirus and solitary LTR. We developed polymerase chain reaction-based assays for seven HML-2 loci and screened 109 human DNA samples from Africa, Europe, Asia, and Southeast Asia. Our results indicate that the diversity of HML-2 elements is higher in African than non-African populations, with population differentiation values ranging from 0.6 to 9.8%. These findings denote a recent expansion from Africa. We compare the phylogenetic relationships of HML-2 sequences that are unique to humans and consider whether these elements have played a role in the remodeling of the hominid genome.
J Mol Evol 2004 Nov
PMID:Allelic variation of HERV-K(HML-2) endogenous retroviral elements in human populations. 1569 20

Recombination enhancer (RE) is essential for regulating donor preference during yeast mating type switching. In this study, by using minichromosome affinity purification (MAP) and mass spectrometry, we found that yeast Ku80p is associated with RE in MATa cells. Chromatin immunoprecipitation assays confirmed its occupancy in vivo. Deletion of YKU80 results in altered chromatin structure in the RE region and more importantly causes a dramatic decrease of HML usage in MATa cells. We also detect directional movement of yKu80p from the RE towards HML during switching. These results indicate a novel function of yeast Ku80p in regulating mating type switching.
Mol Cell Biol 2005 Oct
PMID:The DNA repair protein yKu80 regulates the function of recombination enhancer during yeast mating type switching. 1616 30

We and others recently identified an almost-intact human endogenous retrovirus (HERV), termed HERV-K(HML-2.HOM), that is usually organized as a tandem provirus. Studies on HERV proviral loci commonly rely on the analysis of single alleles being taken as representative for a locus. We investigated the frequency of HERV-K(HML-2.HOM) single and tandem alleles in various human populations. Our analysis revealed that another HERV-K(HML-2) locus, the so-called HERV-K(II) provirus, is also present as a tandem provirus allele in the human population. Proviral tandem formations were identified in various nonhuman primate species. We furthermore examined single nucleotide polymorphisms (SNPs) within the HERV-K(HML-2.HOM) proviral gag, prt, and pol genes, which all result in nonsense mutations. We identified four proviral haplotypes displaying different combinations of gag, prt, and pol SNPs. Haplotypes harboring completely intact proviral genes were not found. For the left provirus of the tandem arrangement a haplotype displaying intact gag and prt genes and a mutated pol was found in about two-thirds of individuals from different ethnogeographic origins. The same haplotype was always found in the right provirus. The various haplotypes point toward multiple recombination events between HERV-K(HML-2.HOM) proviruses. Based on these findings we derive a model for the evolution of the proviral locus since germ line integration.
J Mol Evol 2005 Nov
PMID:Haplotype analysis of the human endogenous retrovirus locus HERV-K(HML-2.HOM) and its evolutionary implications. 1621 23

In Saccharomyces cerevisiae, transcriptional silencing of the cryptic mating loci HML and HMR is established by the combined actions of cis-acting silencers and trans-acting proteins, including Sir2p, Sir3p and Sir4p. The Sir proteins serve as an integral part of a special silent chromatin at the HM loci. Deletion of any of the SIR2-SIR4 genes leads to a complete loss of silencing. However, the SUM1-1 mutation can restore silencing at the HM loci. Recently, it has been shown that Sum1-1p is directed to the silencers and internal regions of the HM loci, and interacts with the Hst1p histone deacetylase that is a paralog of the Sir2p histone deacetylase. Like Sir-dependent silent chromatin, Sum1-1p-dependent chromatin is hypoacetylated. These suggest that Sum1-1p and Hst1p play roles similar to those of the Sir proteins in promoting transcriptional silencing. Here, we examine whether Sum1-1p-dependent chromatin is similar to Sir-dependent silent chromatin, which is characterized by densely and precisely positioned nucleosomes. We demonstrate that Sum1-1p-dependent primary chromatin structure at HMR largely resembles, but is not identical with, Sir-dependent silent chromatin, whereas Sum1-1p-dependent HML chromatin largely resembles, but is not identical with, derepressed chromatin found in a sir- background. This correlates with the previous finding that SUM1-1 restores silencing more efficiently at HMR than at HML. We show also that DNA in Sum1-1p-dependent silent chromatin assumes a distinct topology. Moreover, we present evidence indicating that Sum1-1p can increase the stability of Sir-dependent silent chromatin, thereby providing an explanation for the finding that SUM1-1 enhances HML/HMR silencing in a SIR+ background.
J Mol Biol 2006 Mar 10
PMID:Structural analyses of Sum1-1p-dependent transcriptionally silent chromatin in Saccharomyces cerevisiae. 1640 69

Previous work has shown that the N terminus of the Saccharomyces cerevisiae Sir3 protein is crucial for the function of Sir3 in transcriptional silencing. Here, we show that overexpression of N-terminal fragments of Sir3 in strains lacking the full-length protein can lead to some silencing of HML and HMR. Sir3 contains a BAH (bromo-adjacent homology) domain at its N terminus. Overexpression of this domain alone can lead to silencing as long as Sir1 is overexpressed and Sir2 and Sir4 are present. Overexpression of the closely related Orc1 BAH domain can also silence in the absence of any Sir3 protein. A previously characterized hypermorphic sir3 mutation, D205N, greatly improves silencing by the Sir3 BAH domain and allows it to bind to DNA and oligonucleosomes in vitro. A previously uncharacterized region in the Sir1 N terminus is required for silencing by both the Sir3 and Orc1 BAH domains. The structure of the Sir3 BAH domain has been determined. In the crystal, the molecule multimerizes in the form of a left-handed superhelix. This superhelix may be relevant to the function of the BAH domain of Sir3 in silencing.
Mol Cell Biol 2006 Apr
PMID:Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain. 1658 98

Saccharomyces mating-type switching occurs through a double-strand break-initiated gene conversion event at MAT, using one of two donors located distantly on the same chromosome, HMLalpha and HMRa. MATa cells preferentially choose HMLalpha, a decision that depends on the recombination enhancer (RE) that controls recombination along the left arm of chromosome III. We previously showed that an fhk1Delta mutation reduces HMLalpha usage in MATa cells, but not to the level seen when RE is deleted. We now report that donor preference also depends on binding of the Swi4/Swi6 (SBF) transcription factors to an evolutionarily conserved SCB site within RE. As at other SCB-containing promoters, SBF binds to RE in the G(1) phase. Surprisingly, Fkh1 binds to RE only in G(2), which contrasts with its cell cycle-independent binding to its other target promoters. SBF and Fkh1 define two independent RE activation pathways, as deletion of both Fkh1 and SCB results in nearly complete loss of HML usage in MATa cells. These transcription factors create an epigenetic modification of RE in a fashion that apparently does not involve transcription. In addition, the putative helicase Chl1, previously involved in donor preference, functions in the SBF pathway.
Mol Cell Biol 2006 Jul
PMID:Cell cycle-dependent regulation of Saccharomyces cerevisiae donor preference during mating-type switching by SBF (Swi4/Swi6) and Fkh1. 1680 80

In Saccharomyces cerevisiae, silencers flanking the HML and HMR loci consist of various combinations of binding sites for Abf1p, Rap1p, and the origin recognition complex (ORC) that serve to recruit the Sir silencing complex, thereby initiating the establishment of transcriptionally silent chromatin. There have been seemingly conflicting reports concerning whether silencers function in an orientation-dependent or -independent manner, and what determines the directionality of a silencer has not been explored. We demonstrate that chromatin plays a key role in determining the potency and directionality of silencers. We show that nucleosomes are asymmetrically distributed around the HML-I or HMR-E silencer so that a nucleosome is positioned close to the Abf1p side but not the ORC side of the silencer. This coincides with preferential association of Sir proteins and transcriptional silencing on the Abf1p side of the silencer. Elimination of the asymmetry in nucleosome positioning at a silencer leads to comparable silencing on both sides. Asymmetric nucleosome positioning in the immediate vicinity of a silencer is independent of its orientation and genomic context, indicating that it is the inherent property of the silencer. Moreover, it is also independent of the Sir complex and thus precedes the formation of silent chromatin. Finally, we demonstrate that asymmetric positioning of nucleosomes and directional silencing by a silencer depend on ORC and Abf1p. We conclude that the HML-I and HMR-E silencers promote asymmetric positioning of nucleosomes, leading to unequal potentials of transcriptional silencing on their sides and, hence, directional silencing.
Mol Cell Biol 2006 Oct
PMID:Asymmetric positioning of nucleosomes and directional establishment of transcriptionally silent chromatin by Saccharomyces cerevisiae silencers. 1690 33

Chromatin rearrangement occurs during nucleotide excision repair (NER). Here we show that Snf6 and Snf5, two subunits of the SWI/SNF chromatin-remodeling complex in Saccharomyces cerevisiae, copurify with the NER damage-recognition heterodimer Rad4-Rad23. This interaction between SWI/SNF and Rad4-Rad23 is stimulated by UV irradiation. We demonstrate that NER in the transcriptionally silent, nucleosome-loaded HML locus is reduced in yeast cells lacking functional SWI/SNF. In addition, using a restriction enzyme accessibility assay, we observed UV-induced nucleosome rearrangement at the silent HML locus. Notably, this rearrangement is markedly attenuated when SWI/SNF is inactivated. These results indicate that the SWI/SNF chromatin-remodeling complex is recruited to DNA lesions by damage-recognition proteins to increase DNA accessibility for NER in chromatin.
Nat Struct Mol Biol 2006 Oct
PMID:Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with nucleotide excision repair. 1701 86

We present here a simple, rapid, and extremely flexible technique for the immobilization and visualization of growing yeast cells by epifluorescence microscopy. The technique is equally suited for visualization of static yeast populations, or time courses experiments up to ten hours in length. My microscopy investigates epigenetic inheritance at the silent mating loci in S. cerevisiae. There are two silent mating loci, HML and HMR, which are normally not expressed as they are packaged in heterochromatin. In the sir1 mutant background silencing is weakened such that each locus can either be in the expressed or silenced epigenetic state, so in the population as a whole there is a mix of cells of different epigenetic states for both HML and HMR. My microscopy demonstrated that there is no relationship between the epigenetic state of HML and HMR in an individual cell. sir1 cells stochastically switch epigenetic states, establishing silencing at a previously expressed locus or expressing a previously silenced locus. My time course microscopy tracked individual sir1 cells and their offspring to score the frequency of each of the four possible epigenetic switches, and thus the stability of each of the epigenetic states in sir1 cells. See also Xu et al., Mol. Cell 2006.
 ...
PMID:A rapid technique for the visualization of live immobilized yeast cells. 1870 80


<< Previous 1 2 3 4 5 6 7 8 9 Next >>