scholarly journals Role of Histone Deacetylation in Developmentally Programmed DNA Rearrangements in Tetrahymena thermophila

2002 ◽  
Vol 1 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Sandra Duharcourt ◽  
Meng-Chao Yao
Keyword(s):  
Molecular Mechanisms ◽  
Germ Line ◽  
Trichostatin A ◽  
Chromosome Breakage ◽  
Histone Deacetylation ◽  
Subnuclear Localization ◽  
Dna Elimination ◽  
Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitor Trichostatin

ABSTRACT In Tetrahymena, as in other ciliates, development of the somatic macronucleus during conjugation involves extensive and reproducible rearrangements of the germ line genome, including chromosome fragmentation and excision of internal eliminated sequences (IESs). The molecular mechanisms controlling these events are poorly understood. To investigate the role that histone acetylation may play in the regulation of these processes, we treated Tetrahymena cells during conjugation with the histone deacetylase inhibitor trichostatin A (TSA). We show that TSA treatment induces developmental arrests in the early stages of conjugation but does not significantly affect the progression of conjugation once the mitotic divisions of the zygotic nucleus have occurred. Progeny produced from TSA-treated cells were examined for effects on IES excision and chromosome breakage. We found that TSA treatment caused partial inhibition of excision of five out of the six IESs analyzed but did not affect chromosome breakage at four different sites. TSA treatment greatly delayed in some cells and inhibited in most the excision events in the developing macronucleus. It also led to loss of the specialized subnuclear localization of the chromodomain protein Pdd1p that is normally associated with DNA elimination. We propose a model in which underacetylated nucleosomes mark germ line-limited sequences for excision.

A Histone Deacetylation Inhibitor and Mutant Promote Colony-Type Switching of the Human Pathogen Candida albicans

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 919-924
Author(s):  
A J S Klar ◽  
T Srikantha ◽  
D R Soll
Keyword(s):  
Candida Albicans ◽  
High Frequency ◽  
Trichostatin A ◽  
Histone Deacetylation ◽  
Phenotypic Switching ◽  
Human Pathogen ◽  
Targeted Deletion ◽  
Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
Human Pathogen Candida Albicans

Abstract Most strains of Candida albicans undergo high frequency phenotypic switching. Strain WO-1 undergoes the white-opaque transition, which involves changes in colony and cellular morphology, gene expression, and virulence. We have hypothesized that the switch event involves heritable changes in chromatin structure. To test this hypothesis, we transiently exposed cells to the histone deacetylase inhibitor trichostatin-A (TSA). Treatment promoted a dramatic increase in the frequency of switching from white to opaque, but not opaque to white. Targeted deletion of HDA1, which encodes a deacetylase sensitive to TSA, had the same selective effect. These results support the model that the acetylation of histones plays a selective role in regulating the switching process.

scholarly journals A Novel Chromodomain Protein, Pdd3p, Associates with Internal Eliminated Sequences during Macronuclear Development inTetrahymena thermophila

2000 ◽  
Vol 20 (11) ◽  
pp. 4128-4134 ◽  
Author(s):  
Mikhail A. Nikiforov ◽  
Martin A. Gorovsky ◽  
C. David Allis
Keyword(s):  
De Novo ◽  
Germ Line ◽  
Chromosome Breakage ◽  
Specific Protein ◽  
Developmentally Regulated ◽  
Dna Elimination ◽  
Internal Eliminated Sequences ◽  
Subsequent Elimination ◽  
Rearrangement Processes

ABSTRACT Conversion of the germ line micronuclear genome into the genome of a somatic macronucleus in Tetrahymena thermophila requires several DNA rearrangement processes. These include (i) excision and subsequent elimination of several thousand internal eliminated sequences (IESs) scattered throughout the micronuclear genome and (ii) breakage of the micronuclear chromosomes into hundreds of DNA fragments, followed by de novo telomere addition to their ends. Chromosome breakage sequences (Cbs) that determine the sites of breakage and short regions of DNA adjacent to them are also eliminated. Both processes occur concomitantly in the developing macronucleus. Two stage-specific protein factors involved in germ line DNA elimination have been described previously. Pdd1p and Pdd2p (for programmed DNA degradation) physically associate with internal eliminated sequences in transient electron-dense structures in the developing macronucleus. Here, we report the purification, sequence analysis, and characterization of Pdd3p, a novel developmentally regulated, chromodomain-containing polypeptide. Pdd3p colocalizes with Pdd1p in the peripheral regions of DNA elimination structures, but is also found more internally. DNA cross-linked and immunoprecipitated with Pdd1p- or Pdd3p-specific antibodies is enriched in IESs, but not Cbs, suggesting that different protein factors are involved in elimination of these two groups of sequences.

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