Embryo polarity in moth flies and mosquitoes relies on distinct old genes with localized transcript isoforms

Unrelated genes establish head-to-tail polarity in embryos of different fly species, raising the question of how they evolve this function. We show that in moth flies (Clogmia, Lutzomyia), a maternal transcript isoform of odd-paired (Zic) is localized in the anterior egg and adopted the role of anterior determinant without essential protein change. Additionally, Clogmia lost maternal germ plasm, which contributes to embryo polarity in fruit flies (Drosophila). In culicine (Culex, Aedes) and anopheline mosquitoes (Anopheles), embryo polarity rests on a previously unnamed zinc finger gene (cucoid), or pangolin (dTcf), respectively. These genes also localize an alternative transcript isoform at the anterior egg pole. Basal-branching crane flies (Nephrotoma) also enrich maternal pangolin transcript at the anterior egg pole, suggesting that pangolin functioned as ancestral axis determinant in flies. In conclusion, flies evolved an unexpected diversity of anterior determinants, and alternative transcript isoforms with distinct expression can adopt fundamentally distinct developmental roles.

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Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction

Development ◽

10.1242/dev.113.supplement_2.59 ◽

1991 ◽

Vol 113 (Supplement_2) ◽

pp. 59-62 ◽

Cited By ~ 8

Author(s):

M. Angela Nieto ◽

Leila C. Bradley ◽

David G. Wilkinson

Keyword(s):

Expression Pattern ◽

Zinc Finger ◽

Cell Lineage ◽

Zinc Finger Gene ◽

Early Stages ◽

Cellular Events ◽

Early Expression ◽

Segmental Expression

The zinc-finger gene Krox-20 is expressed in two alternating segments, rhombomeres (r) 3 and 5, in the developing mouse hindbrain. This expression pattern is established prior to rhombomere formation in the mouse, but it is not known how the timing of expression relates to cellular events of segmentation, such as lineage restriction. We have cloned Krox-20 sequences from Xenopus and the chick and shown that its alternating expression pattern is conserved in these systems, suggesting that its role in hindbrain development is conserved. Analysis of the early stages of Krox-20 expression in the chick show that both domains of expression precede the restriction of cell lineage to specific rhombomeres, consistent with a role of this gene in early events of hindbrain segmentation. The finding that expression is not coincident with lineage restriction indicates that early expression may not reflect an irreversible commitment of cells to r3 and r5 and/or may be mosaic.

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Role of Bmznf-2, a Bombyx mori CCCH zinc finger gene, in masculinisation and differential splicing of Bmtra-2

Insect Biochemistry and Molecular Biology ◽

10.1016/j.ibmb.2016.05.008 ◽

2016 ◽

Vol 75 ◽

pp. 32-44 ◽

Cited By ~ 3

Author(s):

Gajula Gopinath ◽

Kallare P. Arunkumar ◽

Kazuei Mita ◽

Javaregowda Nagaraju

Keyword(s):

Bombyx Mori ◽

Zinc Finger ◽

Differential Splicing ◽

Zinc Finger Gene ◽

Ccch Zinc Finger

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The role of the retinoblastoma protein-interacting zinc finger gene 1 tumor suppressor gene in human esophageal squamous cell carcinoma cells

Oncology Letters ◽

10.3892/ol.2013.1608 ◽

2013 ◽

Vol 6 (6) ◽

pp. 1656-1662 ◽

Cited By ~ 11

Author(s):

SHANGWEN DONG ◽

PENG ZHANG ◽

SHAOJIE LIANG ◽

SHUO WANG ◽

PEI SUN ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Suppressor ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Tumor Suppressor Gene ◽

Zinc Finger ◽

Suppressor Gene ◽

Carcinoma Cells ◽

Zinc Finger Gene

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The Role of SINE-VNTR-Alu (SVA) Retrotransposons in Shaping the Human Genome

International Journal of Molecular Sciences ◽

10.3390/ijms20235977 ◽

2019 ◽

Vol 20 (23) ◽

pp. 5977 ◽

Cited By ~ 2

Author(s):

Olympia Gianfrancesco ◽

Bethany Geary ◽

Abigail L. Savage ◽

Kimberley J. Billingsley ◽

Vivien J. Bubb ◽

...

Keyword(s):

Zinc Finger ◽

Zinc Fingers ◽

Cpg Islands ◽

Gene Clusters ◽

Distribution Patterns ◽

Future Research ◽

Zinc Finger Gene ◽

Epigenetic Modulation ◽

Clustering Patterns

Retrotransposons can alter the regulation of genes both transcriptionally and post-transcriptionally, through mechanisms such as binding transcription factors and alternative splicing of transcripts. SINE-VNTR-Alu (SVA) retrotransposons are the most recently evolved class of retrotransposable elements, found solely in primates, including humans. SVAs are preferentially found at genic, high GC loci, and have been termed “mobile CpG islands”. We hypothesise that the ability of SVAs to mobilise, and their non-random distribution across the genome, may result in differential regulation of certain pathways. We analysed SVA distribution patterns across the human reference genome and identified over-representation of SVAs at zinc finger gene clusters. Zinc finger proteins are able to bind to and repress SVA function through transcriptional and epigenetic mechanisms, and the interplay between SVAs and zinc fingers has been proposed as a major feature of genome evolution. We describe observations relating to the clustering patterns of both reference SVAs and polymorphic SVA insertions at zinc finger gene loci, suggesting that the evolution of this network may be ongoing in humans. Further, we propose a mechanism to direct future research and validation efforts, in which the interplay between zinc fingers and their epigenetic modulation of SVAs may regulate a network of zinc finger genes, with the potential for wider transcriptional consequences.

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The role of exon II HTR2A transcript isoforms in the development of mental pathologies and antipsychotic therapy prognosis

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.04.24-26 ◽

2020 ◽

pp. 24-26

Author(s):

М.Н. Грунина ◽

А.М. Заботина ◽

А.С. Журавлев ◽

Р.Ф. Насырова ◽

А.Е. Тараскина

Keyword(s):

Genetic Variant ◽

Therapy Outcome ◽

Gene Transcript ◽

Antipsychotic Therapy ◽

Transcript Isoforms ◽

Alternative Isoforms ◽

Htr2a Gene

Психические расстройства ассоциированы с нарушением паттерна изоформ транскриптов экзона II гена HTR2A за счет преобладания альтернативной изоформы Е2-. При этом высокий уровень экспрессии изоформы Е2- ассоциирован с благоприятным прогнозом антипсихотической терапии. The aim of the study was to analyze the role of exon II HTR2A gene transcript isoforms and rs6311 genetic variant in the development of mental pathologies and antipsychotic therapy prognosis. Alternative isoforms of exon II HTR2A are associated with the development of mental pathologies and is applicable to predict antipsychotic therapy outcome.

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Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽

10.3390/v13061092 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1092

Author(s):

János András Mótyán ◽

Márió Miczi ◽

Stephen Oroszlan ◽

József Tőzsér

Keyword(s):

Amino Acid ◽

Zinc Finger ◽

Cleavage Site ◽

Potential Role ◽

Binding Mode ◽

Interaction Energies ◽

Vitro Assay ◽

Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

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The Only Function of Grauzone Required for Drosophila Oocyte Meiosis Is Transcriptional Activation of the cortex Gene

Genetics ◽

10.1093/genetics/155.4.1831 ◽

2000 ◽

Vol 155 (4) ◽

pp. 1831-1839

Author(s):

Emily Harms ◽

Tehyen Chu ◽

Gwénola Henrion ◽

Sidney Strickland

Keyword(s):

Zinc Finger ◽

Transcriptional Activation ◽

Single Amino Acid ◽

Primary Role ◽

Extra Copy ◽

Oocyte Meiosis ◽

Zinc Finger Motifs ◽

High Level ◽

Transcriptional Pathway

Abstract The grauzone and cortex genes are required for the completion of meiosis in Drosophila oocytes. The grauzone gene encodes a C2H2-type zinc-finger transcription factor that binds to the cortex promoter and is necessary for high-level activation of cortex transcription. Here we define the region of the cortex promoter to which Grauzone binds and show that the binding occurs through the C-terminal, zinc-finger-rich region of the protein. Mutations in two out of the five grauzone alleles result in single amino acid changes within different zinc-finger motifs. Both of these mutations result in the inability of Grauzone to bind DNA effectively. To determine the mechanism by which Grauzone regulates meiosis, transgenic flies were produced with an extra copy of the cortex gene in homozygous grauzone females. This transgene rescued the meiosis arrest of embryos from these mutants and allowed their complete development, indicating that activation of cortex transcription is the primary role of Grauzone during Drosophila oogenesis. These experiments further define a new transcriptional pathway that controls the meiotic cell cycle in Drosophila oocytes.

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From cytopenia to leukemia: the role of Gfi1 and Gfi1b in blood formation

Blood ◽

10.1182/blood-2015-06-655043 ◽

2015 ◽

Vol 126 (24) ◽

pp. 2561-2569 ◽

Cited By ~ 51

Author(s):

Tarik Möröy ◽

Lothar Vassen ◽

Brian Wilkes ◽

Cyrus Khandanpour

Keyword(s):

Zinc Finger ◽

Target Genes ◽

Integration Site ◽

Wide Spectrum ◽

Human Leukemia ◽

Specific Expression ◽

Hematopoietic Stem ◽

Proviral Integration Site ◽

Cell Type Specific Expression

AbstractThe DNA-binding zinc finger transcription factors Gfi1 and Gfi1b were discovered more than 20 years ago and are recognized today as major regulators of both early hematopoiesis and hematopoietic stem cells. Both proteins function as transcriptional repressors by recruiting histone-modifying enzymes to promoters and enhancers of target genes. The establishment of Gfi1 and Gfi1b reporter mice made it possible to visualize their cell type–specific expression and to understand their function in hematopoietic lineages. We now know that Gfi1 is primarily important in myeloid and lymphoid differentiation, whereas Gfi1b is crucial for the generation of red blood cells and platelets. Several rare hematologic diseases are associated with acquired or inheritable mutations in the GFI1 and GFI1B genes. Certain patients with severe congenital neutropenia carry mutations in the GFI1 gene that lead to the disruption of the C-terminal zinc finger domains. Other mutations have been found in the GFI1B gene in families with inherited bleeding disorders. In addition, the Gfi1 locus is frequently found to be a proviral integration site in retrovirus-induced lymphomagenesis, and new, emerging data suggest a role of Gfi1 in human leukemia and lymphoma, underlining the role of both factors not only in normal hematopoiesis, but also in a wide spectrum of human blood diseases.

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