Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes

2012 ◽  
Vol 14 ◽  
Author(s):  
Sam Alsford ◽  
Kelly duBois ◽  
David Horn ◽  
Mark C. Field
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Essential Feature ◽  
Nuclear Architecture ◽  
Gene Products ◽  
Cycle Progression ◽  
Control Of Gene Expression ◽  
African Trypanosomes ◽  
Therapeutic Opportunity ◽  
Major Surface

The control of gene expression, and more significantly gene cohorts, requires tight transcriptional coordination and is an essential feature of probably all cells. In higher eukaryotes, the mechanisms used involve controlled modifications to both local and global DNA environments, principally through changes in chromatin structure as well as cis-element-driven mechanisms. Although the mechanisms regulating chromatin in terms of transcriptional permissiveness and the relation to developmental programmes and responses to the environment are becoming better understood for animal and fungal cells, it is only just beginning to become clear how these processes operate in other taxa, including the trypanosomatids. Recent advances are now illuminating how African trypanosomes regulate higher-order chromatin structure, and, further, how these mechanisms impact on the expression of major surface antigens that are of fundamental importance to life-cycle progression. It is now apparent that several mechanisms are rather more similar between animal and fungal cells and trypanosomes than it originally appeared, but some aspects do involve gene products unique to trypanosomes. Therefore, both evolutionarily common and novel mechanisms cohabit in trypanosomes, offering both important biological insights and possible therapeutic opportunity.

Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function

2000 ◽  
Vol 113 (11) ◽  
pp. 1841-1849 ◽  
Author(s):  
T. Misteli
Keyword(s):  
Gene Expression ◽  
Cell Nucleus ◽  
Cell Biology ◽  
Nuclear Architecture ◽  
Molecular Techniques ◽  
Mrna Splicing ◽  
Cellular Organization ◽  
Control Of Gene Expression ◽  
Expression Of Genes

Gene expression is a fundamental cellular process. The basic mechanisms involved in expression of genes have been characterized at the molecular level. A major challenge is now to uncover how transcription, RNA processing and RNA export are organized within the cell nucleus, how these processes are coordinated with each other and how nuclear architecture influences gene expression and regulation. A significant contribution has come from cell biological approaches, which combine molecular techniques with microscopy methods. These studies have revealed that the mammalian cell nucleus is a complex but highly organized organelle, which contains numerous subcompartments. I discuss here how two essential nuclear processes - transcription and pre-mRNA splicing - are spatially organized and coordinated in vivo, and how this organization might contribute to the control of gene expression. The dynamic nature of nuclear proteins and compartments indicates a high degree of plasticity in the cellular organization of nuclear functions. The cellular organization of transcription and splicing suggest that the morphology of nuclear compartments is largely determined by the activities of the nucleus.

The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3233-3243 ◽  
Author(s):  
X. Cui ◽  
C.Q. Doe
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Lineage ◽  
Temporal Control ◽  
Cycle Progression ◽  
Control Of Gene Expression ◽  
Cell Cycles ◽  
Temporal Regulation ◽  
Intrinsic Gene

The precise temporal control of gene expression is critical for specifying neuronal identity in the Drosophila central nervous system (CNS). A particularly interesting class of genes are those expressed at stereotyped times during the cell lineage of identified neural precursors (neuroblasts): these are termed ‘sublineage’ genes. Although sublineage gene function is vital for CNS development, the temporal regulation of this class of genes has not been studied. Here we show that four genes (ming, even-skipped, unplugged and achaete) are expressed in specific neuroblast sublineages. We show that these neuroblasts can be identified in embryos lacking both neuroblast cytokinesis and cell cycle progression (string mutants) and in embryos lacking only neuroblast cytokinesis (pebble mutants). We find that the unplugged and achaete genes are expressed normally in string and pebble mutant embryos, indicating that temporal control is independent of neuroblast cytokinesis or counting cell cycles. In contrast, neuroblasts require cytokinesis to activate sublineage ming expression, while a single, identified neuroblast requires cell cycle progression to activate even-skipped expression. These results suggest that neuroblasts have an intrinsic gene regulatory hierarchy controlling unplugged and achaete expression, but that cell cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS expression.

scholarly journals A Novel Mechanism of Antagonism between ATP-Dependent Chromatin Remodeling Complexes Regulates RNR3 Expression

2009 ◽  
Vol 29 (12) ◽  
pp. 3255-3265 ◽  
Author(s):  
Raghuvir S. Tomar ◽  
James N. Psathas ◽  
Hesheng Zhang ◽  
Zhengjian Zhang ◽  
Joseph C. Reese
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Large Subunit ◽  
Nucleosome Positioning ◽  
Gene Encoding ◽  
Control Of Gene Expression ◽  
Dna Binding Factors ◽  
Chromatin Remodeling Complexes

ABSTRACT Gene expression depends upon the antagonistic actions of chromatin remodeling complexes. While this has been studied extensively for the enzymes that covalently modify the tails of histones, the mechanism of how ATP-dependent remodeling complexes antagonize each other to maintain the proper level of gene activity is not known. The gene encoding a large subunit of ribonucleotide reductase, RNR3, is regulated by ISW2 and SWI/SNF, complexes that repress and activate transcription, respectively. Here, we studied the functional interactions of these two complexes at RNR3. Deletion of ISW2 causes constitutive recruitment of SWI/SNF, and conditional reexpression of ISW2 causes the repositioning of nucleosomes and reduced SWI/SNF occupancy at RNR3. Thus, ISW2 is required for restriction of access of SWI/SNF to the RNR3 promoter under the uninduced condition. Interestingly, the binding of sequence-specific DNA binding factors and the general transcription machinery are unaffected by the status of ISW2, suggesting that disruption of nucleosome positioning does not cause a nonspecific increase in cross-linking of all factors to RNR3. We provide evidence that ISW2 does not act on SWI/SNF directly but excludes its occupancy by positioning nucleosomes over the promoter. Genetic disruption of nucleosome positioning by other means led to a similar phenotype, linking repressed chromatin structure to SWI/SNF exclusion. Thus, incorporation of promoters into a repressive chromatin structure is essential for prevention of the opportunistic actions of nucleosome-disrupting activities in vivo, providing a novel mechanism for maintaining tight control of gene expression.

Chromatin: Mysteries solved?

2001 ◽  
Vol 79 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Craig L Peterson
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Repair ◽  
Chromatin Structure ◽  
Young Scientist ◽  
Cell Cycle Checkpoints ◽  
Developmental Processes ◽  
Control Of Gene Expression ◽  
The Past

Over the past few years we have seen enormous progress in uncovering the critical roles that chromatin structure has on the control of gene expression, the regulation of developmental processes, and the control of cell cycle checkpoints. No longer is chromatin research the "last bastion of scoundrels." The recent intensity of chromatin research, however, might lead a young scientist to conclude that the field is saturated or that all the big mysteries have been solved. This view could not be further from the truth! Here I briefly outline four areas of chromatin research where new paradigms and mysteries are still waiting to be discovered.Key words: chromatin, DNA repair, SWI/SNF.

scholarly journals Cell Biology of the Trypanosome Genome

2010 ◽  
Vol 74 (4) ◽  
pp. 552-569 ◽  
Author(s):  
Jan-Peter Daniels ◽  
Keith Gull ◽  
Bill Wickstead
Keyword(s):  
Gene Expression ◽  
Cell Biology ◽  
Nuclear Organization ◽  
Nuclear Architecture ◽  
Gene Clusters ◽  
Model Organisms ◽  
Protein Coding ◽  
African Trypanosomes ◽  
Protein Coding Genes ◽  
A Genome

SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

scholarly journals Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions

1999 ◽  
Vol 13 (9001) ◽  
Author(s):  
Gary S. Stein ◽  
André J. Van Wijnen ◽  
Janet L. Stein ◽  
Jane B. Lian ◽  
Shirwin H. Pockwinse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Architecture ◽  
Control Of Gene Expression ◽  
Microgravity Conditions ◽  
And Control

scholarly journals Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Davide Seruggia ◽  
Almudena Fernández ◽  
Marta Cantero ◽  
Ana Fernández-Miñán ◽  
José Luis Gomez-Skarmeta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Regulatory Sequences ◽  
Cell Type ◽  
Chromosome Conformation ◽  
Control Of Gene Expression ◽  
Cell Type Specific

Abstract Control of gene expression is dictated by cell-type specific regulatory sequences that physically organize the structure of chromatin, including promoters, enhancers and insulators. While promoters and enhancers convey cell-type specific activating signals, insulators prevent the cross-talk of regulatory elements within adjacent loci and safeguard the specificity of action of promoters and enhancers towards their targets in a tissue specific manner. Using the mouse tyrosinase (Tyr) locus as an experimental model, a gene whose mutations are associated with albinism, we described the chromatin structure in cells at two distinct transcriptional states. Guided by chromatin structure, through the use of Chromosome Conformation Capture (3C), we identified sequences at the 5′ and 3′ boundaries of this mammalian gene that function as enhancers and insulators. By CRISPR/Cas9-mediated chromosomal deletion, we dissected the functions of these two regulatory elements in vivo in the mouse, at the endogenous chromosomal context, and proved their mechanistic role as genomic insulators, shielding the Tyr locus from the expression patterns of adjacent genes.

Turnover of Gene Products in the Control of Gene Expression

BioScience ◽  
1982 ◽  
Vol 32 (3) ◽  
pp. 181-184 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee
Keyword(s):  
Gene Expression ◽  
Gene Products ◽  
Control Of Gene Expression
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