scholarly journals Recombination and disjunction in female germ cells of Drosophila depend on the germline activity of the gene sex-lethal

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5785-5794 ◽  
Author(s):  
D. Bopp ◽  
C. Schutt ◽  
J. Puro ◽  
H. Huang ◽  
R. Nothiger
Keyword(s):  
Ectopic Expression ◽  
Common Mechanism ◽  
Germline Development ◽  
Homologous Chromosomes ◽  
Male Germline ◽  
High Incidence ◽  
Germline Expression ◽  
Sex Lethal ◽  
Female Specific ◽  
Dominant Suppressor

Gametogenesis in males and females differs in many ways. An important difference in Drosophila is that recombination between homologous chromosomes occurs only in female meiosis. Here, we report that this process relies on the correct functioning of Sex-lethal (Sxl) which is primarily known as the master gene in somatic sex determination. Certain alleles of this gene (Sxl(fs)) disrupt the germline, but not the somatic function of Sxl and cause an arrest of germ cell development during cystocyte proliferation. Using dominant suppressor mutations that relieve this early block in Sxl(fs) mutant females, we discovered additional requirements of Sxl for normal meiotic differentiation of the oocyte. Females mutant for Sxl(fs) and carrying a suppressor become fertile, but pairing of homologous chromosomes and formation of chiasmata is severely perturbed, resulting in an almost complete lack of recombinants and a high incidence of non-disjunction events. Similar results were obtained when germline expression of wild-type Sxl was compromised by mutations in virilizer (vir), a positive regulator of Sxl. Ectopic expression of a Sxl transgene in premeiotic stages of male germline development, on the other hand, is not sufficient to allow recombination to take place, which suggests that Sxl does not have a discriminatory role in this female-specific process. We propose that Sxl performs at least two tasks in oogenesis: an ‘early’ function in formation of the egg chamber, and a ‘late’ function in progression of the meiotic cell cycle, suggesting that both events are coordinated by a common mechanism.

scholarly journals SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in C. elegans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Charlotte P Choi ◽  
Rebecca J Tay ◽  
Margaret R Starostik ◽  
Suhua Feng ◽  
James J Moresco ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ectopic Expression ◽  
Sexually Dimorphic ◽  
Small Nuclear Rna ◽  
Germline Development ◽  
C Elegans ◽  
Male Germline ◽  
Nuclear Rna ◽  
Specific Regulation ◽  
Male Specific

Piwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a male germline-enriched variant of a conserved subunit of the small nuclear RNA-activating protein complex, as a male-specific piRNA transcription factor in Caenorhabditis elegans. SNPC-1.3 colocalizes with the core piRNA transcription factor, SNPC-4, in nuclear foci of the male germline. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires SNPC-4. Loss of snpc-1.3 leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to the snpc-1.3 promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression of snpc-1.3 and male piRNAs during oogenesis. Thus, sexually dimorphic regulation of snpc-1.3 expression coordinates male and female piRNA expression during germline development.

scholarly journals Regulation of behavioral and pheromonal aspects of sex determination in Drosophila melanogaster by the Sex-lethal gene.

Genetics ◽  
1989 ◽  
Vol 123 (3) ◽  
pp. 535-541 ◽  
Author(s):  
L Tompkins ◽  
S P McRobert
Keyword(s):  
Drosophila Melanogaster ◽  
Sexual Behavior ◽  
Sex Determination ◽  
Ectopic Expression ◽  
Lethal Gene ◽  
Gene Products ◽  
Morphological Aspects ◽  
Sex Lethal ◽  
Normal Males ◽  
Female Specific

Abstract We have shown that the Sex-lethal (Sxl) gene, which controls morphological aspects of sex determination in Drosophila melanogaster, also regulates sexual behavior. Chromosomal males that are hemizygous for a deletion of the entire Sxl locus perform normal courtship and synthesize the two courtship-inhibiting pheromones that normal males make. However, ectopic expression of female-specific Sex-lethal gene products drastically alters chromosomal males' ability to perform and elicit courtship and increases the probability that they will synthesize a courtship-stimulating pheromone or fail to synthesize one of the inhibitory pheromones. These observations suggest that male sexual behavior is a consequence of the Sxl gene's being functionally inactive in haplo-X flies.

Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5033-5048 ◽  
Author(s):  
J.H. Hager ◽  
T.W. Cline
Keyword(s):  
Sex Determination ◽  
Germ Cells ◽  
Rna Splicing ◽  
Feedback Loop ◽  
Dose Effect ◽  
Male Germ Cells ◽  
Control Female ◽  
Sex Lethal ◽  
Specific Regulation ◽  
Female Specific

With a focus on Sex-lethal (Sxl), the master regulator of Drosophila somatic sex determination, we compare the sex determination mechanism that operates in the germline with that in the soma. In both cell types, Sxl is functional in females (2X2A) and nonfunctional in males (1X2A). Somatic cell sex is determined initially by a dose effect of X:A numerator genes on Sxl transcription. Once initiated, the active state of SXL is maintained by a positive autoregulatory feedback loop in which Sxl protein insures its continued synthesis by binding to Sxl pre-mRNA and thereby imposing the productive (female) splicing mode. The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control. Here we show that an increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells. These snf+ dose effects are as dramatic as those of X:A numerator genes on Sxl in the soma and qualify snf as a numerator element of the X:A signal for Sxl in the germline. We also show that female-specific regulation of Sxl in the germline involves a positive autoregulatory feedback loop on RNA splicing, as it does in the soma. Neither a phenotypically female gonadal soma nor a female dose of X chromosomes in the germline is essential for the operation of this feedback loop, although a female X-chromosome dose in the germline may facilitate it. Engagement of the Sxl splicing feedback loop in somatic cells invariably imposes female development. In contrast, engagement of the Sxl feedback loop in male germ cells does not invariably disrupt spermatogenesis; nevertheless, it is premature to conclude that Sxl is not a switch gene in germ cells for at least some sex-specific aspects of their differentiation. Ironically, the testis may be an excellent organ in which to study the interactions among regulatory genes such as Sxl, snf, ovo and otu which control female-specific processes in the ovary.

scholarly journals Genomic and cDNA selection-amplification identifies transcriptome-wide binding sites for the Drosophila protein sex-lethal

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250592
Author(s):  
Hiren Banerjee ◽  
Ravinder Singh
Keyword(s):  
Binding Sites ◽  
Binding Proteins ◽  
Rna Binding ◽  
Developmental Stages ◽  
Rna Binding Proteins ◽  
Systematic Analysis ◽  
Downstream Targets ◽  
Drosophila Protein ◽  
Sex Lethal ◽  
Female Specific

Background Downstream targets for a large number of RNA-binding proteins remain to be identified. The Drosophila master sex-switch protein Sex-lethal (SXL) is an RNA-binding protein that controls splicing, polyadenylation, or translation of certain mRNAs to mediate female-specific sexual differentiation. Whereas some targets of SXL are known, previous studies indicate that additional targets of SXL have escaped genetic screens. Methodology/Principal findings Here, we have used an alternative molecular approach of GEnomic Selective Enrichment of Ligands by Exponential enrichment (GESELEX) using both the genomic DNA and cDNA pools from several Drosophila developmental stages to identify new potential targets of SXL. Our systematic analysis provides a comprehensive view of the Drosophila transcriptome for potential SXL-binding sites. Conclusion/Significance We have successfully identified new SXL-binding sites in the Drosophila transcriptome. We discuss the significance of our analysis and that the newly identified binding sites and sequences could serve as a useful resource for the research community. This approach should also be applicable to other RNA-binding proteins for which downstream targets are unknown.

scholarly journals Mutations in Caenorhabditis elegans him-19 Show Meiotic Defects That Worsen with Age

2010 ◽  
Vol 21 (6) ◽  
pp. 885-896 ◽  
Author(s):  
Lois Tang ◽  
Thomas Machacek ◽  
Yasmine M. Mamnun ◽  
Alexandra Penkner ◽  
Jiradet Gloggnitzer ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Male Meiosis ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Protein ◽  
High Incidence ◽  
Bivalent Formation ◽  
Synaptonemal Complex Formation

From a screen for meiotic Caenorhabditis elegans mutants based on high incidence of males, we identified a novel gene, him-19, with multiple functions in prophase of meiosis I. Mutant him-19(jf6) animals show a reduction in pairing of homologous chromosomes and subsequent bivalent formation. Consistently, synaptonemal complex formation is spatially restricted and possibly involves nonhomologous chromosomes. Also, foci of the recombination protein RAD-51 occur delayed or cease altogether. Ultimately, mutation of him-19 leads to chromosome missegregation and reduced offspring viability. The observed defects suggest that HIM-19 is important for both homology recognition and formation of meiotic DNA double-strand breaks. It therefore seems to be engaged in an early meiotic event, resembling in this respect the regulator kinase CHK-2. Most astonishingly, him-19(jf6) hermaphrodites display worsening of phenotypes with increasing age, whereas defects are more severe in female than in male meiosis. This finding is consistent with depletion of a him-19-dependent factor during the production of oocytes. Further characterization of him-19 could contribute to our understanding of age-dependent meiotic defects in humans.

scholarly journals MicroRNA in Cervical Cancer: OncomiRs and Tumor Suppressor miRs in Diagnosis and Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Kouji Banno ◽  
Miho Iida ◽  
Megumi Yanokura ◽  
Iori Kisu ◽  
Takashi Iwata ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Diagnosis And Treatment ◽  
Investigation Methods ◽  
Incidence And Mortality ◽  
High Incidence ◽  
Female Specific

Cervical cancer is a female-specific disease with a high incidence and mortality. MicroRNAs (miRNAs) are implicated in posttranscriptional regulation of gene expression and in the pathogenic mechanisms of cancer, suggesting their importance in diagnosis and treatment. miRNAs may have roles in the pathogenesis of cervical cancer based on the increases or decreases in several specific miRNAs found in patients with this disease. The miRNAs implicated in cervical cancer are miR-21, miR-126, and miR-143, and clinical application of these miRNAs for diagnosis and treatment is under investigation. Methods for diagnosis of cervical cancer include analysis of changes in the levels of specific miRNAs in serum and determination of aberrant hypermethylation of miRNAs. Supplementation of miR-143 or inhibition of miR-21 activityin vivomay be therapeutic strategy for cervical cancer. Previous approaches to development of siRNA as a drug have provided information for establishment of therapy based on these approaches, and an anti-miR-21 inhibitor has been developed. miRNAs also have effects on drug resistance and may be useful in combination therapy with other drugs.

scholarly journals Phosphorus-insufficient maternal milk is associated with ectopic expression of collagen I and female-specific bony changes in infant mouse cartilages

2015 ◽  
Vol 1 ◽  
pp. 5-10 ◽  
Author(s):  
Akihiro Nakamura ◽  
Kenji Miyado ◽  
Michiyo Nasu ◽  
Tomohiro Kono ◽  
Akihiro Umezawa
Keyword(s):  
Ectopic Expression ◽  
Collagen I ◽  
Maternal Milk ◽  
Infant Mouse ◽  
Female Specific

scholarly journals TWO CLOSELY LINKED MUTATIONS IN DROSOPHILA MELANOGASTER THAT ARE LETHAL TO OPPOSITE SEXES AND INTERACT WITH DAUGHTERLESS

Genetics ◽  
1978 ◽  
Vol 90 (4) ◽  
pp. 683-697
Author(s):  
Thomas W Cline
Keyword(s):  
Maternal Effect ◽  
Spontaneous Mutation ◽  
Dominant Male ◽  
Lethal Effects ◽  
Male Specific Lethal ◽  
Constitutive Mutation ◽  
Sex Lethal ◽  
The Right ◽  
Female Specific ◽  
Male Specific

ABSTRACT A new spontaneous mutation named Sex-lethal, Male-specific #1 (SxlM1) is described that is lethal to males, even in the presence of an Sxl  + duplication. Females homozygous for SxlM1 are fully viable. This dominant, male-specific lethal mutation is on the X chromosome approximately 0.007 map units to the right of a previously isolated female-specific mutation, Female-lethal, here renamed Sex-lethal, Female-specific #1 (SxlF1). SxlM1 and SxlF1 are opposite in nearly every respect, particularly with regard to their interaction with the maternal effect of the autosomal mutation, daughterless (da). Females that are homozygous for da produce defective eggs that cannot support female (XX) development. A single dose of SxlM1 enables daughters to survive this da female-specific lethal maternal effect. A duplication of the Sxl locus weakly mimics this action of SxlM1. In contrast, SxlF1 and a deficiency for Sxl, strongly enhance the female-lethal effects of da. The actions of SxlM1 and SxlF1 are explained by a model in which expression of the Sxl locus is essential for females, lethal for males, and under the control of a product of the da locus. It is suggested that SxlM1 is a constitutive mutation at the Sxl locus.

scholarly journals Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer

2020 ◽  
Author(s):  
Sylvan C. Baca ◽  
David Y. Takeda ◽  
Ji-Heui Seo ◽  
Justin Hwang ◽  
Sheng Yu Ku ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Modifications ◽  
Ectopic Expression ◽  
Resistance Mechanism ◽  
Regulatory Elements ◽  
Common Mechanism ◽  
Enhancer Activity ◽  
Adaptive Resistance ◽  
Neuroendocrine Prostate Cancer ◽  
A Cell

AbstractLineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer1,2. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens. To investigate the epigenomic basis of this resistance mechanism, we profiled histone modifications in NEPC and PRAD patient-derived xenografts (PDXs) using chromatin immunoprecipitation and sequencing (ChIP-seq). We identified a vast network of cis-regulatory elements (N~15,000) that are recurrently activated in NEPC. The FOXA1 transcription factor (TF), which pioneers androgen receptor (AR) chromatin binding in the prostate epithelium3,4, is reprogrammed to NE-specific regulatory elements in NEPC. Despite loss of dependence upon AR, NEPC maintains FOXA1 expression and requires FOXA1 for proliferation and expression of NE lineage-defining genes. Ectopic expression of the NE lineage TFs ASCL1 and NKX2-1 in PRAD cells reprograms FOXA1 to bind to NE regulatory elements and induces enhancer activity as evidenced by histone modifications at these sites. Our data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying novel cancer dependencies through epigenomic profiling.

Sign in / Sign up

Export Citation Format

Share Document