scholarly journals 255.Dnmt3L: a coordinator of epigenetic modifications during spermatogenesis

2004 ◽  
Vol 16 (9) ◽  
pp. 255
Author(s):  
K. E. Webster ◽  
M. K. O'Bryan ◽  
U. Aapola ◽  
P. E. Crewther ◽  
R. Lyle ◽  
...  
Keyword(s):  
Epigenetic Modifications ◽  
Histone Deacetylation ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Imprinted Genes ◽  
Targeted Disruption ◽  
Biallelic Expression ◽  
Homologous Chromosomes ◽  
Progressive Degeneration ◽  
Chromosome Alignment

Spermatogenesis is a process with unique epigenetic requirements. The differentiation from diploid spermatogonia to haploid spermatozoa requires regulation of genomic imprint establishment, stage specific gene expression, meiotic division, and the histone-protamine transition. The methyltransferase regulator, Dnmt3L, is expressed during gametogenesis and is necessary for establishment of maternal methylation imprints in the oocyte. Targeted disruption of Dnmt3L does not appear to affect oogenesis, as mature oocytes are generated, however resultant heterozygous progeny die mid gestation due to biallelic expression of imprinted genes. Dnmt3L–/– males however show spermatogenic arrest. We found that this arrest occurs during prophase I of meiosis, with spermatocytes lost by both apoptosis and germ cell sloughing. A progressive degeneration ensues, resulting in a Sertoli cell phenotype. Electron microscopy of meiotic spermatocytes revealed that homologous chromosomes fail to align and form synaptonemal complexes. Furthermore, Dnmt3L–/– spermatocytes show abnormal methylation on paternally imprinted genes and abnormal global retention of histone acetylation, implicating Dnmt3L in histone deacetylase recruitment. Thus, during spermatogenesis, Dnmt3L is crucial for two distinct epigenetic modifications; imprint establishment and global histone deacetylation prior to homologous chromosome alignment. The latter defect is likely to affect the alignment of homologous chromosomes and trigger the pachytene checkpoint leading to spermatocyte death. Since Dnmt3L has no DNA methlytransferase or HDAC activity itself, we propose that Dnmt3L is essential for the coordination of epigenetic layers, at least during spermatogenesis.

scholarly journals Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma results in receptor-specific alterations in retinoic acid-mediated differentiation and retinoic acid metabolism.

1995 ◽  
Vol 15 (2) ◽  
pp. 843-851 ◽  
Author(s):  
J F Boylan ◽  
T Lufkin ◽  
C C Achkar ◽  
R Taneja ◽  
P Chambon ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Specific Gene ◽  
Cell Type ◽  
Targeted Disruption ◽  
F9 Cells ◽  
Retinoid Receptors ◽  
Alpha Gene ◽  
Polar Derivatives ◽  
Crabp Ii

F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell type called extraembryonic endoderm when treated with retinoic acid (RA), a derivative of retinol (vitamin A). This differentiation is presumably mediated through the actions of retinoid receptors, the RARs and RXRs. To delineate the functions of each of the different retinoid receptors in this model system, we have generated F9 cell lines in which both copies of either the RAR alpha gene or the RAR gamma gene are disrupted by homologous recombination. The absence of RAR alpha is associated with a reduction in the RA-induced expression of both the CRABP-II and Hoxb-1 (formerly 2.9) genes. The absence of RAR gamma is associated with a loss of the RA-inducible expression of the Hoxa-1 (formerly Hox-1.6), Hoxa-3 (formerly Hox-1.5), laminin B1, collagen IV (alpha 1), GATA-4, and BMP-2 genes. Furthermore, the loss of RAR gamma is associated with a reduction in the metabolism of all-trans-RA to more polar derivatives, while the loss of RAR alpha is associated with an increase in metabolism of RA relative to wild-type F9 cells. Thus, each of these RARs exhibits some specificity with respect to the regulation of differentiation-specific gene expression. These results provide an explanation for the expression of multiple RAR types within one cell type and suggest that each RAR has specific functions.

scholarly journals High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta

BMC Genetics ◽  
2010 ◽  
Vol 11 (1) ◽  
pp. 25 ◽  
Author(s):  
Caroline Daelemans ◽  
Matthew E Ritchie ◽  
Guillaume Smits ◽  
Sayeda Abu-Amero ◽  
Ian M Sudbery ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
Specific Gene ◽  
Imprinted Genes ◽  
High Throughput Analysis ◽  
Human Term Placenta ◽  
Throughput Analysis ◽  
Term Placenta ◽  
Specific Gene Expression ◽  
Allele Specific

scholarly journals Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

2020 ◽  
Author(s):  
Spencer G. Gordon ◽  
Lisa E. Kursel ◽  
Kewei Xu ◽  
Ofer Rog
Keyword(s):  
Synaptonemal Complex ◽  
Sequence Homology ◽  
Genetic Information ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Local Sequence ◽  
Chromosome Alignment ◽  
Dimerization Interface

AbstractDuring sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.

The abundant retinal protein of the Chlamydomonas eye is not the photoreceptor for phototaxis and photophobic responses

2001 ◽  
Vol 114 (21) ◽  
pp. 3857-3863
Author(s):  
Markus Fuhrmann ◽  
Alke Stahlberg ◽  
Elena Govorunova ◽  
Simone Rank ◽  
Peter Hegemann
Keyword(s):  
Green Alga ◽  
Transcriptional Gene Silencing ◽  
Specific Gene ◽  
Related Protein ◽  
Wild Type ◽  
Targeted Disruption ◽  
Retinal Protein ◽  
Post Transcriptional Gene Silencing ◽  
Unicellular Green Alga ◽  
Efficient Reduction

The chlamyopsin gene (cop) encodes the most abundant eyespot protein in the unicellular green alga Chlamydomonas reinhardtii. This opsin-related protein (COP) binds retinal and was thought to be the photoreceptor controlling photomovement responses via a set of photoreceptor currents. Unfortunately, opsin-deficient mutants are not available and targeted disruption of non-selectable nuclear genes is not yet possible in any green alga. Here we show that intron-containing gene fragments directly linked to their intron-less antisense counterpart provide efficient post-transcriptional gene silencing (PTGS) in C. reinhardtii, thus allowing an efficient reduction of a specific gene product in a green alga. In opsin-deprived transformants, flash-induced photoreceptor currents (PC) are left unchanged. Moreover, photophobic responses as studied by motion analysis and phototaxis tested in a light-scattering assay were indistinguishable from the responses of untransformed wild-type cells. We conclude that phototaxis and photophobic responses in C. reinhardtii are triggered by an as yet unidentified rhodopsin species.

Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2273-2282 ◽  
Author(s):  
W. Dean ◽  
L. Bowden ◽  
A. Aitchison ◽  
J. Klose ◽  
T. Moore ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Es Cells ◽  
Embryonic Stem ◽  
Upstream Region ◽  
Imprinted Genes ◽  
Epigenetic Alterations ◽  
Es Cell ◽  
Biallelic Expression

In vitro manipulation of preimplantation mammalian embryos can influence differentiation and growth at later stages of development. In the mouse, culture of embryonic stem (ES) cells affects their totipotency and may give rise to fetal abnormalities. To investigate whether this is associated with epigenetic alterations in imprinted genes, we analysed two maternally expressed genes (Igf2r, H19) and two paternally expressed genes (Igf2, U2af1-rs1) in ES cells and in completely ES cell-derived fetuses. Altered allelic methylation patterns were detected in all four genes, and these were consistently associated with allelic changes in gene expression. All the methylation changes that had arisen in the ES cells persisted on in vivo differentiation to fetal stages. Alterations included loss of methylation with biallelic expression of U2af1-rs1, maternal methylation and predominantly maternal expression of Igf2, and biallelic methylation and expression of Igf2r. In many of the ES fetuses, the levels of H19 expression were strongly reduced, and this biallelic repression was associated with biallellic methylation of the H19 upstream region. Surprisingly, biallelic H19 repression was not associated with equal levels of Igf2 expression from both parental chromosomes, but rather with a strong activation of the maternal Igf2 allele. ES fetuses derived from two of the four ES lines appeared developmentally compromised, with polyhydramnios, poor mandible development and interstitial bleeding and, in chimeric fetuses, the degree of chimerism correlated with increased fetal mass. Our study establishes a model for how early embryonic epigenetic alterations in imprinted genes persist to later developmental stages, and are associated with aberrant phenotypes.

scholarly journals Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ana J. Chucair-Elliott ◽  
Sarah R. Ocañas ◽  
David R. Stanford ◽  
Victor A. Ansere ◽  
Kyla B. Buettner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Affinity Purification ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Tissue Level ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.

scholarly journals EFG1 Null Mutants of Candida albicansSwitch but Cannot Express the Complete Phenotype of White-Phase Budding Cells

2000 ◽  
Vol 182 (6) ◽  
pp. 1580-1591 ◽  
Author(s):  
Thyagarajan Srikantha ◽  
Luong K. Tsai ◽  
Karla Daniels ◽  
David R. Soll
Keyword(s):  
Phase Cell ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Phenotypic Characteristics ◽  
Transcription Start Sites ◽  
Daughter Cells ◽  
White Phase ◽  
Rapid Amplification ◽  
Mutant Cells ◽  
Null Mutants

ABSTRACT The Candida albicans gene EFG1 encodes a putative trans-acting factor. In strain WO-1, which undergoes the white-opaque transition, EFG1 is transcribed as a 3.2-kb mRNA in white-phase cells and a less-abundant 2.2-kb mRNA in opaque-phase cells. cDNA sequencing and 5′ rapid amplification of cDNA ends analysis demonstrate that the major difference in molecular mass of the two transcripts is due to different transcription start sites. EFG1 null mutants form opaque-phase colonies and express the opaque-phase cell phenotype at 25°C. When shifted from 25 to 42°C, mutant opaque-phase cells undergo phenotypic commitment to the white phase, which includes deactivation of the opaque-phase-specific gene OP4 and activation of the white-phase-specific gene WH11, as do wild-type opaque-phase cells. After the commitment event, EFG1 null mutant cells form daughter cells which have the smooth (pimpleless) surface of white-phase cells but the elongate morphology of opaque-phase cells. Taken together, these results demonstrate thatEFG1 expression is not essential for the switch event per se, but is essential for a subset of phenotypic characteristics necessary for the full expression of the phenotype of white-phase cells. These results demonstrate that EFG1 is not the site of the switch event, but is, rather, downstream of the switch event.

A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36

Blood ◽  
2009 ◽  
Vol 113 (5) ◽  
pp. 1053-1061 ◽  
Author(s):  
Tiemo Katzenberger ◽  
Jörg Kalla ◽  
Ellen Leich ◽  
Heike Stöcklein ◽  
Elena Hartmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Growth Pattern ◽  
Expression Profiles ◽  
Growth Patterns ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Non Hodgkin Lymphoma ◽  
Diffuse Growth

Abstract Follicular lymphoma (FL) is a morphologically and genetically well-characterized B-cell non-Hodgkin lymphoma that can show predominantly follicular, combined follicular and diffuse, or predominantly diffuse growth patterns. Although approximately 85% of FLs harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FLs are less well characterized on the phenotypical, molecular, and clinical level. We studied 35 predominantly diffuse FL by immunohistochemistry, classical chromosome banding analysis, fluorescence in situ hybridization (FISH), and gene expression profiling. A total of 28 of 29 analyzable cases lacked t(14;18), and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FLs were grade 1 and 23 were grade 2, and the immunophenotype with frequent expression of CD10, BCL6, and CD23 was in line with a germinal center B-cell phenotype. The gene expression profiles of 4 predominantly diffuse FLs fell into the spectrum of typical FL, with a unique enrichment of specific gene signatures. Remarkably, patients with diffuse FL frequently presented with low clinical stage and large but localized inguinal tumors. These results suggest that predominantly diffuse FL represent a distinct subtype of t(14;18)-negative nodal FL with a unifying genetic alteration (deletion of 1p36) and characteristic clinical features.

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