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Daniel E. Gottschling

Bio: Daniel E. Gottschling is an academic researcher from Fred Hutchinson Cancer Research Center. The author has contributed to research in topics: Gene & Saccharomyces cerevisiae. The author has an hindex of 49, co-authored 79 publications receiving 14753 citations. Previous affiliations of Daniel E. Gottschling include University of Illinois at Chicago & University of Colorado Boulder.


Papers
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Journal ArticleDOI
01 Nov 1982-Cell
TL;DR: It is proposed that the IVS portion of the RNA has several enzyme-like properties that enable it to break and reform phosphodiester bonds and that enzymes, small nuclear RNAs and folding of the pre-rRNA into an RNP are unnecessary for these reactions.

2,077 citations

Journal ArticleDOI
16 Nov 1990-Cell
TL;DR: Yeast telomeres exert a position effect on the transcription of nearby genes, an effect that is under epigenetic control as demonstrated by phenotype and mRNA analyses.

1,379 citations

Journal ArticleDOI
TL;DR: A genome-wide chromatin structure analysis in a higher eukaryote found a binary pattern of histone modifications among euchromatic genes, with active genes being hyperacetylated for H3 and H4 and hypermethylated at Lys 4 and Lys 79 of H3, and inactive genes being hypomethylated and deacetylation at the same residues.
Abstract: The covalent modification of nucleosomal histones has emerged as a major determinant of chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation and methylation, we performed a genome-wide chromatin structure analysis in a higher eukaryote. We found a binary pattern of histone modifications among euchromatic genes, with active genes being hyperacetylated for H3 and H4 and hypermethylated at Lys 4 and Lys 79 of H3, and inactive genes being hypomethylated and deacetylated at the same residues. Furthermore, the degree of modification correlates with the level of transcription, and modifications are largely restricted to transcribed regions, suggesting that their regulation is tightly linked to polymerase activity.

849 citations

Journal ArticleDOI
14 Jun 2002-Cell
TL;DR: DOT1 was originally identified as a gene affecting telomeric silencing in S. cerevisiae, but it is found that Dot1p methylates histone H3 on lysine 79, which maps to the top and bottom of the nucleosome core.

840 citations

Journal ArticleDOI
21 Oct 1994-Science
TL;DR: The discovery of TLC1 confirms the existence of telomerase in S. cerevisiae and may facilitate both the analysis of this enzyme and an understanding of telomere structure and function.
Abstract: Telomeres, the natural ends of linear eukaryotic chromosomes, are essential for chromosome stability. Because of the nature of DNA replication, telomeres require a specialized mechanism to ensure their complete duplication. Telomeres are also capable of silencing the transcription of genes that are located near them. In order to identify genes in the budding yeast Saccharomyces cerevisiae that are important for telomere function, a screen was conducted for genes that, when expressed in high amounts, would suppress telomeric silencing. This screen lead to the identification of the gene TLC1 (telomerase component 1). TLC1 encodes the template RNA of telomerase, a ribonucleoprotein required for telomere replication in a variety of organisms. The discovery of TLC1 confirms the existence of telomerase in S. cerevisiae and may facilitate both the analysis of this enzyme and an understanding of telomere structure and function.

770 citations


Cited by
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Journal ArticleDOI
23 Feb 2007-Cell
TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.

10,046 citations

Journal ArticleDOI
18 May 2007-Cell
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.

6,488 citations

Journal ArticleDOI
TL;DR: In this paper, a simple and efficient method for synthesizing pure single stranded RNAs of virtually any structure is described, based on the unusually specific RNA synthesis by bacteriophage SP6 RNA polymerase which initiates transcription exclusively at an SP6 promoter.
Abstract: A simple and efficient method for synthesizing pure single stranded RNAs of virtually any structure is described. This in vitro transcription system is based on the unusually specific RNA synthesis by bacteriophage SP6 RNA polymerase which initiates transcription exclusively at an SP6 promoter. We have constructed convenient cloning vectors that contain an SP6 promoter immediately upstream from a polylinker sequence. Using these SP6 vectors, optimal conditions have been established for in vitro RNA synthesis. The advantages and uses of SP6 derived RNAs as probes for nucleic acid blot and solution hybridizations are demonstrated. We show that single stranded RNA probes of a high specific activity are easy to prepare and can significantly increase the sensitivity of nucleic acid hybridization methods. Furthermore, the SP6 transcription system can be used to prepare RNA substrates for studies on RNA processing (1,5,9) and translation (see accompanying paper).

5,732 citations

Journal ArticleDOI
01 Nov 2002-Science
TL;DR: The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).
Abstract: Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.

3,565 citations

Journal ArticleDOI
30 Jan 1998-Yeast
TL;DR: A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed and will reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications.
Abstract: A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed. These strains minimize or eliminate the homology to the corresponding marker genes in commonly used vectors without significantly affecting adjacent gene expression. Because the homology between commonly used auxotrophic marker gene segments and genomic sequences has been largely or completely abolished, these strains will also reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications. We also report the construction of new members of the pRS400 series of vectors, containing the kanMX, ADE2 and MET15 genes.

3,448 citations