scholarly journals Homologue Pairing in Flies and Mammals: Gene Regulation When Two Are Involved

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Manasi S. Apte ◽  
Victoria H. Meller
Keyword(s):  
Gene Expression ◽  
Chromosome Segregation ◽  
Germ Cells ◽  
Developmentally Regulated ◽  
X Chromosomes ◽  
Disease States ◽  
Genome Regulation ◽  
Normal Expression ◽  
Normal Pairing

Chromosome pairing is usually discussed in the context of meiosis. Association of homologues in germ cells enables chromosome segregation and is necessary for fertility. A few organisms, such as flies, also pair their entire genomes in somatic cells. Most others, including mammals, display little homologue pairing outside of the germline. Experimental evidence from both flies and mammals suggests that communication between homologues contributes to normal genome regulation. This paper will contrast the role of pairing in transmitting information between homologues in flies and mammals. In mammals, somatic homologue pairing is tightly regulated, occurring at specific loci and in a developmentally regulated fashion. Inappropriate pairing, or loss of normal pairing, is associated with gene misregulation in some disease states. While homologue pairing in flies is capable of influencing gene expression, the significance of this for normal expression remains unknown. The sex chromosomes pose a particularly interesting situation, as females are able to pair X chromosomes, but males cannot. The contribution of homologue pairing to the biology of the X chromosome will also be discussed.

The Phenotype of mes-2, mes-3, mes-4 and mes-6, Maternal-Effect Genes Required for Survival of the Germline in Caenorhabditis elegans, Is Sensitive to Chromosome Dosage

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 167-185 ◽  
Author(s):  
Carol Garvin ◽  
Richard Holdeman ◽  
Susan Strome
Keyword(s):  
Gene Expression ◽  
Germ Cells ◽  
Maternal Effect ◽  
Early Embryo ◽  
Male Offspring ◽  
X Chromosomes ◽  
Control Of Gene Expression ◽  
Maternal Effect Genes ◽  
Surprising Finding

AbstractMutations in mes-2, mes-3, mes-4, and mes-6 result in maternal-effect sterility: hermaphrodite offspring of mes/mes mothers are sterile because of underproliferation and death of the germ cells, as well as an absence of gametes. Mutant germ cells do not undergo programmed cell death, but instead undergo a necrotic-type death, and their general poor health apparently prevents surviving germ cells from forming gametes. Male offspring of mes mothers display a significantly less severe germline phenotype than their hermaphrodite siblings, and males are often fertile. This differential response of hermaphrodite and male offspring to the absence of mes+ product is a result of their different X chromosome compositions; regardless of their sexual phenotype, XX worms display a more severe germline phenotype than XO worms, and XXX worms display the most severe phenotype. The sensitivity of the mutant phenotype to chromosome dosage, along with the similarity of two MES proteins to chromatin-associated regulators of gene expression in Drosophila, suggest that the essential role of the mes genes is in control of gene expression in the germline. An additional, nonessential role of the mes genes in the soma is suggested by the surprising finding that mutations in the mes genes, like mutations in dosage compensation genes, feminize animals whose male sexual identity is somewhat ambiguous. We hypothesize that the mes genes encode maternally supplied regulators of chromatin structure and gene expression in the germline and perhaps in somatic cells of the early embryo, and that at least some of their targets are on the X chromosomes.

Effects of ten–eleven translocation 1 (Tet1) on DNA methylation and gene expression in chicken primordial germ cells

2019 ◽  
Vol 31 (3) ◽  
pp. 509 ◽  
Author(s):  
Minli Yu ◽  
Dongfeng Li ◽  
Wanyan Cao ◽  
Xiaolu Chen ◽  
Wenxing Du
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Germ Cells ◽  
Dna Methyltransferase ◽  
Primordial Germ Cells ◽  
Dna Demethylation ◽  
Caveolin 1 ◽  
Expression Of Genes ◽  
Deleted In Azoospermia

Ten–eleven translocation 1 (Tet1) is involved in DNA demethylation in primordial germ cells (PGCs); however, the precise regulatory mechanism remains unclear. In the present study the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in developing PGCs and the role of Tet1 in PGC demethylation were analysed. Results show that 5mC levels dropped significantly after embryonic Day 4 (E4) and 5hmC levels increased reaching a peak at E5–E5.5. Interestingly, TET1 protein was highly expressed during E5 to E5.5, which showed a consistent trend with 5hmC. The expression of pluripotency-associated genes (Nanog, PouV and SRY-box 2 (Sox2)) and germ cell-specific genes (caveolin 1 (Cav1), piwi-like RNA-mediated gene silencing 1 (Piwi1) and deleted in azoospermia-like (Dazl)) was upregulated after E5, whereas the expression of genes from the DNA methyltransferase family was decreased. Moreover, the Dazl gene was highly methylated in early PGCs and then gradually hypomethylated. Knockdown of Tet1 showed impaired survival and proliferation of PGCs, as well as increased 5mC levels and reduced 5hmC levels. Further analysis showed that knockdown of Tet1 led to elevated DNA methylation levels of Dazl and downregulated gene expression including Dazl. Thus, this study reveals the dynamic epigenetic reprogramming of chicken PGCs invivo and the molecular mechanism of Tet1 in regulating genomic DNA demethylation and hypomethylation of Dazl during PGC development.

scholarly journals The role of vitamins and minerals in modulating the expression of microRNA

2014 ◽  
Vol 27 (1) ◽  
pp. 94-106 ◽  
Author(s):  
Emma L. Beckett ◽  
Zoe Yates ◽  
Martin Veysey ◽  
Konsta Duesing ◽  
Mark Lucock
Keyword(s):  
Gene Expression ◽  
Food Sources ◽  
Transcriptional Level ◽  
Disease States ◽  
Regulatory Circuit ◽  
Non Coding Rna ◽  
Epigenetic Machinery ◽  
Health And Disease ◽  
Expression Potential

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

scholarly journals DAZL regulates mRNA deadenylation independently of translation in germ cells

2021 ◽  
Author(s):  
Richard W. P. Smith ◽  
Barbara Gorgoni ◽  
Zoë C. Johnston ◽  
William A. Richardson ◽  
Kelsey M. Grieve ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cells ◽  
Mrna Translation ◽  
Aberrant Gene Expression ◽  
Mechanistic Analysis ◽  
Deleted In Azoospermia ◽  
Aberrant Gene ◽  
Mutually Independent ◽  
Mrna Fate

ABSTRACTAberrant gene expression during gametogenesis is one of the factors underlying infertility, which affects roughly 15% of couples worldwide. Deleted-in-Azoospermia-Like (DAZL), a member of the DAZ-gene family, encodes an mRNA-specific regulator of translation which is essential for gametogenesis in both sexes. In this study we show that DAZL controls gene expression in oocytes by regulating the length of the mRNA poly(A) tail, a major determinant of temporal and amplitudinal gene regulation in germ cells, in which gene expression is regulated entirely post-transcriptionally. We show that DAZL does not induce polyadenylation but that binding of DAZL efficiently inhibits mRNA deadenylation induced by oocyte maturation. We reveal that this activity depends on DAZL-mediated recruitment of poly(A)-binding protein, PABP, to the mRNA. Although DAZL also activates mRNA translation via PABP recruitment, mechanistic analysis revealed that neither translation nor translational activation are required for DAZL to stabilise the poly(A) tail, suggesting two mutually independent posttranscriptional roles for the DAZL-PABP complex. We show that recruited PABP must maintain its ability to bind RNA, leading to a model in which DAZL recruits PABP and/or stabilises PABP binding to poly(A) thereby preventing access of deadenylases. These results indicate that the role of DAZL in regulating germ-cell mRNA fate is more complex than previously thought and inform on the poorly understood links between mRNA translation and deadenylation, showing that they can be mechanistically separable.

scholarly journals First person – Victor Palacios

2021 ◽  
Vol 134 (7) ◽  
Keyword(s):  
Chromosome Segregation ◽  
Germ Cells ◽  
Medical Center ◽  
Early Career ◽  
First Person ◽  
University Of Texas ◽  
Early Career Researchers ◽  
The University ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Victor Palacios is first author on ‘Importin-9 regulates chromosome segregation and packaging in Drosophila germ cells’, published in JCS. Victor conducted his PhD research in the lab of Michael Buszczak at the University of Texas Southwestern Medical Center, Dallas, TX, where he investigated the essential role of Importin-9 in Drosophila fertility.

Harnessing targeted DNA methylation and demethylation using dCas9

2019 ◽  
Vol 63 (6) ◽  
pp. 813-825 ◽  
Author(s):  
Christian Pflueger ◽  
Tessa Swain ◽  
Ryan Lister
Keyword(s):  
Dna Methylation ◽  
Disease Modeling ◽  
Aberrant Methylation ◽  
Dna Modification ◽  
Future Directions ◽  
Disease States ◽  
Genome Regulation ◽  
Fundamental Understanding ◽  
Functional Relevance

Abstract DNA methylation is an essential DNA modification that plays a crucial role in genome regulation during differentiation and development, and is disrupted in a range of disease states. The recent development of CRISPR/catalytically dead CRISPR/Cas9 (dCas9)-based targeted DNA methylation editing tools has enabled new insights into the roles and functional relevance of this modification, including its importance at regulatory regions and the role of aberrant methylation in various diseases. However, while these tools are advancing our ability to understand and manipulate this regulatory layer of the genome, they still possess a variety of limitations in efficacy, implementation, and targeting specificity. Effective targeted DNA methylation editing will continue to advance our fundamental understanding of the role of this modification in different genomic and cellular contexts, and further improvements may enable more accurate disease modeling and possible future treatments. In this review, we discuss strategies, considerations, and future directions for targeted DNA methylation editing.

scholarly journals Fetal estrogens are not involved in sex determination but critical for early ovarian differentiation in rabbits

Endocrinology ◽  
2021 ◽  
Author(s):  
Geneviève Jolivet ◽  
Nathalie Daniel-Carlier ◽  
Erwana Harscoët ◽  
Eloïse Airaud ◽  
Aurélie Dewaele ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Determination ◽  
Germ Cells ◽  
Ovarian Reserve ◽  
Sexual Differentiation ◽  
Primordial Follicles ◽  
Ovarian Differentiation ◽  
Estrogen Synthesis ◽  
Proliferation And Differentiation

Abstract AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated. To elucidate the role of this peak, we produced three lines of TALEN genetically edited CYP19A1 KO rabbits, that were devoid of any estradiol production. All the KO XX rabbits developed as females with aberrantly small-sized ovaries in adulthood, an almost empty reserve of primordial follicles and very few large antrum follicles. Ovulation never occurred. Our histological, immunohistological and transcriptomic analyses showed that the estradiol surge in the XX fetal rabbit gonad is not essential to its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for establishment of the ovarian reserve.

scholarly journals A role for chromatin topology in imprinted domain regulation

2016 ◽  
Vol 94 (1) ◽  
pp. 43-55 ◽  
Author(s):  
William A. MacDonald ◽  
Saqib S. Sachani ◽  
Carlee R. White ◽  
Mellissa R.W. Mann
Keyword(s):  
Gene Expression ◽  
Nuclear Architecture ◽  
Monoallelic Expression ◽  
X Chromosomes ◽  
Genome Wide ◽  
Topologically Associated Domains ◽  
Development And Differentiation ◽  
Imprint Domain ◽  
First Time

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

scholarly journals PhenotypeXpression: sub-classification of disease states using public gene expression data and literature

2018 ◽  
Author(s):  
Lucy Lu Wang ◽  
Huaiying Lin ◽  
Xiaojun Bao ◽  
Subhajit Sengupta ◽  
Ben Busby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Disease Classification ◽  
Expression Data ◽  
Phenotypic Profile ◽  
Disease States ◽  
Impact On Treatment ◽  
Differential Gene ◽  
Disease Subtypes

AbstractThe success of personalized medicine relies on proper disease classification and subtyping. Differential gene expression among disease subtypes can have a significant impact on treatment effect. This complicates the role of clinicians seeking more tailored diagnoses in cases where granular disease subtypes are not well defined. PhenotypeXpression (PhenoX) is a tool for rapid disease subtyping using publicly available gene expression data and literature. PhenoX aggregates and clusters gene expression data to determine potential disease subtypes, and develops a phenotypic profile for each subtype using term co-occurrences in published literature. Although the availability of public gene expression data is limited, we are able to observe clearly defined subtypes for several conditions.

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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