Regulation of fission yeast mating-type interconversion by chromosome imprinting

Development ◽  
1990 ◽  
Vol 108 (Supplement) ◽  
pp. 3-8
Author(s):  
Amar J. S. Klar
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Cell Lineage ◽  
Specific Pattern ◽  
Type Locus ◽  
A Cell ◽  
Cell Switches ◽  
Chromosome Imprinting ◽  
A Site

Mating types of the fission yeast Schizosaccharomyces pombe interchange nonrandomly in a cell lineage so that only one cell among four granddaughters of a cell ever switches, and the sister of the newly switched cell switches efficiently in consecutive cell divisions, thereby producing chains of recurrent switching. The programme of cellular differentiation is mediated by inheritance of parental DNA chains at the mating type locus (mat1) by progeny cells. This review summarizes recent results suggesting that two types of imprinting events at the mat1 locus are required to generate the specific pattern of switching in a cell lineage. One of those is a site- and strand- specific event that is required before the mat1 locus can be cleaved in vivo. The other is a double-stranded break at mat1 that is healed by gene conversion in the progeny cells resulting in switching the mat1 locus.

scholarly journals The mechanism of fission yeast mating type interconversion: seal/replicate/cleave model of replication across the double-stranded break site at mat1.

Genetics ◽  
1991 ◽  
Vol 127 (3) ◽  
pp. 489-496 ◽  
Author(s):  
A J Klar ◽  
M J Bonaduce ◽  
R Cafferkey
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Dna Cleavage ◽  
Cell Lineage ◽  
Type Locus ◽  
Cis Acting ◽  
Cell Divisions ◽  
Break Site ◽  
A Cell ◽  
Cell Switches

Abstract The interconversion of cell type in the fission yeast, Schizosaccharomyces pombe, is initiated by a double-stranded break (DSB) found at the mating type locus (mat1). A heritable site- and strand-specific DNA "imprinting" event at mat1 was recently hypothesized to be required to make the mat1 locus cleavable, and the DSB was suggested to be produced one generation before the actual switching event. It is known that only one cell among four granddaughters of a cell ever switches, and the sister of the recently switched cell switches efficiently in consecutive cell divisions. The feature of consecutive switching creates a major difficulty of having to replicate chromosomes possessing the DSB. The mat1 cis-acting leaky mutation, called smt-s, reduces the level of the DSB required for switching and is shown here to be a 27-bp deletion located 50 bp away from the cut site. Determination of the pattern and frequency of switching of the mutant allele by cell lineage studies has allowed us to conclude the following: (1) the chromosome with the DSB is sealed and replicated, then one of the specific chromatids is cleaved again to generate switching-competent cells in consecutive cell divisions and (2) the smt-s mutation affects DNA cleavage and not the hypothesized DNA imprinting step.

scholarly journals Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4349-4357 ◽  
Author(s):  
Fanny Guimont-Desrochers ◽  
Geneviève Boucher ◽  
Zhongjun Dong ◽  
Martine Dupuis ◽  
André Veillette ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Adoptive Transfer ◽  
Nk Cell ◽  
Cell Lineage ◽  
Current View ◽  
Antitumoral Activity ◽  
Nk Cell Differentiation ◽  
A Cell

Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.

scholarly journals The fission yeast heterochromatin protein Rik1 is required for telomere clustering during meiosis

2004 ◽  
Vol 165 (6) ◽  
pp. 759-765 ◽  
Author(s):  
Creighton T. Tuzon ◽  
Britta Borgstrom ◽  
Dietmar Weilguny ◽  
Richard Egel ◽  
Julia Promisel Cooper ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Sexual Differentiation ◽  
Histone H3 ◽  
Heterochromatin Protein ◽  
Type Locus ◽  
Heterochromatin Formation ◽  
Mating Type Locus ◽  
Telomere Protein ◽  
Chromosome Movements

Telomeres share the ability to silence nearby transcription with heterochromatin, but the requirement of heterochromatin proteins for most telomere functions is unknown. The fission yeast Rik1 protein is required for heterochromatin formation at centromeres and the mating-type locus, as it recruits the Clr4 histone methyltransferase, whose modification of histone H3 triggers binding by Swi6, a conserved protein involved in spreading of heterochromatin. Here, we demonstrate that Rik1 and Clr4, but not Swi6, are required along with the telomere protein Taz1 for crucial chromosome movements during meiosis. However, Rik1 is dispensable for the protective roles of telomeres in preventing chromosome end-fusion. Thus, a Swi6-independent heterochromatin function distinct from that at centromeres and the mating-type locus operates at telomeres during sexual differentiation.

scholarly journals cAMP-Responsive Element Binding Protein: A Vital Link in Embryonic Hormonal Adaptation

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2208-2221 ◽  
Author(s):  
Maria Schindler ◽  
Sünje Fischer ◽  
René Thieme ◽  
Bernd Fischer ◽  
Anne Navarrete Santos
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Binding Protein ◽  
Cell Lineage ◽  
Element Binding Protein ◽  
A Cell ◽  
Responsive Element ◽  
Camp Responsive Element Binding

Abstract The transcription factor cAMP responsive element-binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival. One of the CREB target genes is adiponectin, which acts synergistically with insulin. We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards, CREB and ATF1, ATF3, and ATF4 are present with increasing expression for CREB, ATF1, and ATF3 during gastrulation and with a dominant expression in the embryoblast (EB). In vitro stimulation with insulin and IGF-I reduced CREB and ATF1 transcripts by approximately 50%, whereas CREB phosphorylation was increased. Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor (adipoR)1 expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium. Embryonic CREB expression was altered in a cell lineage-specific pattern. Although in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells. In TB, adiponectin expression was increased (diabetic 427.8 ± 59.3 pg/mL vs normoinsulinaemic 143.9 ± 26.5 pg/mL), whereas it was no longer measureable in the EB. Analysis of embryonic adipoRs showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal cross talk before implantation in a cell lineage-specific manner. Embryonic CREB/ATFs act as insulin/IGF sensors. Lack of insulin is compensated by a CREB-mediated adiponectin expression, which may maintain glucose uptake in blastocysts grown in diabetic mothers.

scholarly journals The Mating-Type Proteins of Fission Yeast Induce Meiosis by Directly Activating mei3 Transcription

1998 ◽  
Vol 18 (12) ◽  
pp. 7317-7326 ◽  
Author(s):  
Willem J. van Heeckeren ◽  
David R. Dorris ◽  
Kevin Struhl
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Regulatory Element ◽  
Single Gene ◽  
Homeodomain Protein ◽  
Type Locus ◽  
Mating Type Locus ◽  
Positive Elements ◽  
Tata Sequence ◽  
Multiple Sequences

ABSTRACT Cell type control of meiotic gene regulation in the budding yeastSaccharomyces cerevisiae is mediated by a cascade of transcriptional repressors, a1-α2 and Rme1. Here, we investigate the analogous regulatory pathway in the fission yeastSchizosaccharomyces pombe by analyzing the promoter ofmei3, the single gene whose expression is sufficient to trigger meiosis. The mei3 promoter does not appear to contain a negative regulatory element that represses transcription in haploid cells. Instead, correct regulation of mei3transcription depends on a complex promoter that contains at least five positive elements upstream of the TATA sequence. These elements synergistically activate mei3 transcription, thereby constituting an on-off switch for the meiosis pathway. Element C is a large region containing multiple sequences that resemble binding sites for Mc, an HMG domain protein encoded by the mating-type locus. The function of element C is extremely sensitive to spacing changes but not to linker-scanning mutations, suggesting the possibility that Mc functions as an architectural transcription factor. Altered-specificity experiments indicate that element D interacts with Pm, a homeodomain protein encoded by the mating-type locus. This indicates that Pm functions as a direct activator of the meiosis pathway, whereas the homologous mating-type protein in S. cerevisiae (α2) functions as a repressor. Thus, despite the strong similarities between the mating-type loci of S. cerevisiae and S. pombe, the regulatory logic that governs the tight control of the key meiosis-inducing genes in these organisms is completely different.

scholarly journals swi6, a gene required for mating-type switching, prohibits meiotic recombination in the mat2-mat3 "cold spot" of fission yeast.

Genetics ◽  
1991 ◽  
Vol 129 (4) ◽  
pp. 1033-1042
Author(s):  
A J Klar ◽  
M J Bonaduce
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Meiotic Recombination ◽  
Hot Spot ◽  
Strand Break ◽  
Double Strand Break ◽  
Cold Spot ◽  
Additional Result ◽  
Type Locus ◽  
Mating Type Switching

Abstract Mitotic interconversion of the mating-type locus (mat1) of the fission yeast Schizosaccharomyces pombe is initiated by a double-strand break at mat1. The mat2 and mat3 loci act as nonrandom donors of genetic information for mat1 switching such that switches occur primarily (or only) to the opposite mat1 allele. Location of the mat1 "hot spot" for transposition should be contrasted with the "cold spot" of meiotic recombination located within the adjoining mat2-mat3 interval. That is, meiotic interchromosomal recombination in mat2, mat3 and the intervening 15-kilobase region does not occur at all. swi2 and swi6 switching-deficient mutants possess the normal level of double-strand break at mat1, yet they fail to switch efficiently. By testing for meiotic recombination in the cold spot, we found the usual lack of recombination in a swi2 mutant but a significant level of recombination in a swi6 mutant. Therefore, the swi6 gene function is required to keep the donor loci inert for interchromosomal recombination. This finding, combined with the additional result that switching primarily occurs intrachromosomally, suggests that the donor loci are made accessible for switching by folding them onto mat1, thus causing the cold spot of recombination.

The clr1 locus regulates the expression of the cryptic mating-type loci of fission yeast.

Genetics ◽  
1992 ◽  
Vol 131 (2) ◽  
pp. 287-296 ◽  
Author(s):  
G Thon ◽  
A J Klar
Keyword(s):  
Fission Yeast ◽  
Mating Type ◽  
Cold Spot ◽  
Type Region ◽  
Type Locus ◽  
Silent Genes ◽  
The Right ◽  
Chromosome Ii ◽  
Donor Locus ◽  
Type Information

Abstract The mat2-P and mat3-M loci of fission yeast contain respectively the plus (P) and minus (M) mating-type information in a transcriptionally silent state. That information is transposed from the mat2 or mat3 donor locus via recombination into the expressed mating-type locus (mat1) resulting in switching of the cellular mating type. We have identified a gene, named clr1 (for cryptic loci regulator), whose mutations allow expression of the mat2 and mat3 loci. clr1 mutants undergo aberrant haploid meiosis, indicative of transcription of the silent genes. Production of mRNA from mat3 is detectable in clr1 mutants. Furthermore, the ura4 gene inserted near mat3, weakly expressed in wild-type cells, is derepressed in clr1 mutants. The clr1 mutations also permit meiotic recombination in the 15-kb mat2-mat3 interval, where recombination is normally inhibited. The clr1 locus is in the right arm of chromosome II. We suggest that clr1 regulates silencing of the mat2 and mat3 loci, and participates in establishing the "cold spot" for recombination by organizing the chromatin structure of the mating-type region.

scholarly journals A role for apoptosis-inducing factor in T cell development

2012 ◽  
Vol 209 (9) ◽  
pp. 1641-1653 ◽  
Author(s):  
Hridesh Banerjee ◽  
Abhishek Das ◽  
Smita Srivastava ◽  
Hamid R. Mattoo ◽  
Krishnamurthy Thyagarajan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Metabolism ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Deficient Mutant ◽  
Oxidoreductase Activity ◽  
A Cell ◽  
B Lineage ◽  
Apoptosis Inducing Factor

Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T cell receptor β recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding–deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity–deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic β-selection.

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