scholarly journals Genetic interactions of histone acetyl-transferase enzymes encoding genes Gcn5 and Mof with hsrω lncRNA gene

2019 ◽  
Author(s):  
Deo Prakash Chaturvedi
Keyword(s):  
X Chromosome ◽  
Transgene Expression ◽  
Distribution Patterns ◽  
Histone Acetyl Transferase ◽  
Down Regulation ◽  
Lncrna Gene ◽  
Over Expression ◽  
Specific Localization ◽  
H4k16 Acetylation ◽  
Male Specific

AbstractThe hsrω lncRNAs are known to interact with the Iswi chromatin remodeler while Iswi is known to interact with Gcn5, a general histone acetyl transferase, and Mof, a male-specific HAT essential for H4K16 acetylation and consequent hyperactivity of the single X-chromosome in male Drosophila. We show here that hsrω genetically interacts with Gcn5 as well as Mof, but unlike the suppression of phenotypes due to down-regulation or absence of Iswi, those following down-regulation of Gcn5 or Mof are suppressed by over-expression of hsrω. General lethality caused by Act-GAL4 driven global expression of Gcn5-RNAi and the male-specific lethality following Mof-RNAi transgene expression were partially suppressed by over-expression of hsrω, but not by down regulation through hsrω-RNAi. Likewise, eye phenotypes following ey-GAL4 driven down-regulation of Gcn5 or Mof were also partially suppressed by over-expression of hsrω. Act-GAL4 driven global over-expression of hsrω along with Gcn5-RNAi transgene substantially restored levels of Gcn5 RNA as well as protein that were reduced by Gcn5-RNAi. Mof-RNAi transgene expression reduced Megator and Msl-2 levels and their nuclear distribution patterns; over-expression of hsrω along with Mof-RNAi substantially restored Megator levels and its distribution at the nuclear rim and in nucleoplasmic speckles and at the same time restored the male X-chromosome specific localization of Msl-2. Earlier reported antagonistic interactions of Mof with Iswi and interaction of hsrω transcripts with Megator appear to underlie the suppression of Gcn5 and Mof phenotypes by over-expression of the lncRNAs. Present results add the dosage compensation pathway to the list of diverse pathways in which the multiple lncRNAs produced by the hsrω are known to have important roles.

scholarly journals Interactions between dosage compensation complex components Msl-1, Msl-2 and NURF component NURF301 with long non-coding RNA gene hsrω

2019 ◽  
Author(s):  
Deo Prakash Chaturvedi
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Dosage Compensation Complex ◽  
Chromatin Remodeler ◽  
Down Regulation ◽  
Over Expression ◽  
Non Coding Rna ◽  
Crucial Component ◽  
Male Specific ◽  
Long Non Coding Rna

AbstractHyperactivity of the single X-chromosome in male Drosophila is achieved by establishing a ribonucleoprotein complex, called Dosage Compensation Complex (DCC), on the male X chromosome. Msl-1 and Msl-2 proteins, involved in the initiation and establishing of DCC on male X chromosome, are very crucial component of this complex. In the present study, it has been found here that a long non-coding RNA gene hsrω genetically interacts with Msl-1 as well as Msl-2 and suppresses the lethal phenotype of Msl-1 or Msl-2 down-regulation in its up-regulated background. Additionally, it is also found here that an ATP-dependent chromatin remodeler, NURF301, also interacts with hsrω in same manner. General lethality caused by Act-GAL4 driven global expression of NURF301-RNAi and the male-specific lethality following Msl-1-RNAi or Msl-2-RNAi transgene expression were partially suppressed by over-expression of hsrω, but not by down regulation through hsrω-RNAi. Likewise, eye phenotypes following ey-GAL4 driven down-regulation of NURF301 or Msl-1 or Msl-2 were also partially suppressed by over-expression of hsrω. Act-GAL4 driven global over-expression of hsrω along with Msl-1-RNAi or Msl-2-RNAi transgene substantially restored levels of MSL-2 protein on the male X chromosome. Similarly, levels and distribution of Megator protein, which was reduced and distribution at nuclear rim and in nucleoplasm was affected in the MT and SG nuclei, is also restored when hsrω transcripts are down-regulated in Act-GAL4 driven Msl-1-RNAi or Msl-2-RNAi genetic background. NURF301, a known chromatin remodeler, when down-regulated shows decondensed X chromosome in male larvae. Down-regulation of hsrω results in restoration of chromosome architecture without affecting the level of ISWI protein-another chromatin remodeler protein, known to interacting with hsrω.

scholarly journals Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoma Ota ◽  
Makoto Hayashi ◽  
Shumpei Morita ◽  
Hiroki Miura ◽  
Satoru Kobayashi
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Primordial Germ Cells ◽  
Histone H4 ◽  
X Chromosomes ◽  
Essential Components ◽  
Msl Complex ◽  
Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3245-3258 ◽  
Author(s):  
G.J. Bashaw ◽  
B.S. Baker
Keyword(s):  
Dna Binding ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Ring Finger ◽  
The Other ◽  
Male Specific Lethal ◽  
Alternatively Spliced ◽  
Sex Lethal ◽  
Specific Regulation ◽  
Male Specific

In Drosophila dosage compensation increases the rate of transcription of the male's X chromosome and depends on four autosomal male-specific lethal genes. We have cloned the msl-2 gene and shown that MSL-2 protein is co-localized with the other three MSL proteins at hundreds of sites along the male polytene X chromosome and that this binding requires the other three MSL proteins. msl-2 encodes a protein with a putative DNA-binding domain: the RING finger. MSL-2 protein is not produced in females and sequences in both the 5′ and 3′ UTRs are important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is alternatively spliced in a Sex-lethal-dependent fashion in its 5′ UTR.

scholarly journals macroH2A1 Histone Variants Are Depleted on Active Genes but Concentrated on the Inactive X Chromosome

2006 ◽  
Vol 26 (12) ◽  
pp. 4410-4420 ◽  
Author(s):  
Lakshmi N. Changolkar ◽  
John R. Pehrson
Keyword(s):  
X Chromosome ◽  
Distribution Patterns ◽  
Detailed Examination ◽  
Histone Variants ◽  
Heterochromatin Protein ◽  
Inactive X Chromosome ◽  
Preferential Localization ◽  
Intergenic Regions ◽  
Liver Chromatin ◽  
Active Genes

ABSTRACT Using a novel thiol affinity chromatography approach to purify macroH2A1-containing chromatin fragments, we examined the distribution of macroH2A1 histone variants in mouse liver chromatin. We found that macroH2A1 was depleted on the transcribed regions of active genes. This depletion was observed on all of the 20 active genes that we probed, with only one site showing a small amount of enrichment. In contrast, macroH2A1 was concentrated on the inactive X chromosome, consistent with our previous immunofluorescence studies. This preferential localization was seen on genes that are active in liver, genes that are inactive in liver, and intergenic regions but was absent from four regions that escape X inactivation. These results support the hypothesis that macroH2As function as transcriptional repressors. Also consistent with this hypothesis is our finding that the heterochromatin protein HP1β copurifies with the macroH2A1-containing chromatin fragments. This study presents the first detailed examination of the distribution of macroH2A1 variants on specific sequences. Our results indicate that macroH2As have complex distribution patterns that are influenced by both local factors and long-range mechanisms.

Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1825-1832 ◽  
Author(s):  
Barbara P Rattner ◽  
Victoria H Meller
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
X Chromosome ◽  
Specific Expression ◽  
Linked Gene ◽  
Male And Female ◽  
Male Specific Lethal ◽  
Msl Complex ◽  
Male Specific ◽  
Rox Rna

Abstract The MSL complex of Drosophila upregulates transcription of the male X chromosome, equalizing male and female X-linked gene expression. Five male-specific lethal proteins and at least one of the two noncoding roX RNAs are essential for this process. The roX RNAs are required for the localization of MSL complexes to the X chromosome. Although the mechanisms directing targeting remain speculative, the ratio of MSL protein to roX RNA influences localization of the complex. We examine the transcriptional regulation of the roX genes and show that MSL2 controls male-specific roX expression in the absence of any other MSL protein. We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome.

scholarly journals MicroRNAs in mouse models of lymphoid malignancies

2010 ◽  
Vol 1 (1) ◽  
pp. 8 ◽  
Author(s):  
Nicola A. O. Zanesi ◽  
Yuri Pekarsky ◽  
Francesco Trapasso ◽  
George Calin ◽  
Carlo M. Croce
Keyword(s):  
Gene Expression ◽  
Mouse Models ◽  
Gene Expression Regulation ◽  
Human Leukemia ◽  
Down Regulation ◽  
Over Expression ◽  
Lymphoid Malignancies ◽  
Knockout Animals ◽  
Mouse Modeling

<!--StartFragment--> <p class="MsoBodyText"><span style="mso-tab-count: 1;"> </span>The discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation that affects many normal and pathologic biological systems. Among the malignancies affected by the dysregulation of miRNAs there are cancers of lymphoid origin, in which miRNAs are thought to have tumor suppressive or tumor promoting activities, depending on the nature of their specific targets. In the last 4-5 years, the experimental field that provided the deepest insights into the <em>in vivo</em><span style="font-style: normal;"> biology of miRNAs is that of mouse modeling in which transgenic and knockout animals mimic, respectively, over-expression or down-regulation of specific miRNAs involved in human leukemia/lymphoma. This review discusses recent advances in our understanding of lymphoid malignancies based on the natural and engineered mouse models of three different miRNAs, miR-15a/16-1 cluster, miR-155, and miR-17-92 cluster.</span></p> <!--EndFragment-->

scholarly journals MicroRNA-101 inhibits growth and metastasis of human ovarian cancer cells by targeting PI3K/AKT

2021 ◽  
Vol 17 (1) ◽  
pp. 127-134
Author(s):  
Min Wei ◽  
Hongjuan Jin ◽  
ShuLi Yang ◽  
Zhuo Li ◽  
Xinlei Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Pten Expression ◽  
Cell Cycle Analysis ◽  
Ovarian Cancer Cells ◽  
G1 Arrest ◽  
Down Regulation ◽  
Over Expression

IntroductionOvarian cancer is the most frequent cause of gynecological cancer related mortality in woman. This study was designed to investigate the role and therapeutic potential of miRNA-101 in ovarian cancer.Material and methodsExpression analysis was carried out by real-time quantitative polymerase chain reaction. Transfections were performed with the help of Lipofectamine 2000 reagent. AO/EB and annexin V/PI staining was used to detect apoptosis and flow cytometry was used for cell cycle analysis. Western blotting was employed for cell cycle analysis.ResultsIt was found that miRNA-101 was significantly down-regulated in ovarian cancer cells. The over-expression of miRNA-101 causes a significant decrease in the viability of ovarian cancer cells via the initiation of apoptosis and sub-G1 arrest of OVACAR-3 cells. It was indicated that PTEN was the potential target of miRNA-101 in OVACAR-3 cells. There was 4.5-fold up-regulation of PTEN expression in ovarian cancer cell lines and the over-expression of miRNA-101 in OVACAR-3 cells resulted in the down-regulation of PTEN expression. The inhibition of PTEN in the OVACAR-3 cells arrested the proliferation of these cells. The over-expression of miRNA-101 causes significant down-regulation in PI3K and AKT expression of OVACAR-3 cells.ConclusionsIt can be concluded that miRNA-101 acts as a tumor suppressor which may be beneficial in the treatment of ovarian cancer.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1

2017 ◽  
Vol 398 (7) ◽  
pp. 785-792 ◽  
Author(s):  
Jian-Hui Chen ◽  
Yu-Long Zheng ◽  
Chuan-Qin Xu ◽  
Li-Zhi Gu ◽  
Zong-Li Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Valproic Acid ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Down Regulation ◽  
Over Expression ◽  
Protein Levels

Abstract Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to −100 and −166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

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