scholarly journals CDK-regulated phase separation seeded by histone genes ensures precise growth and function of Histone Locus Bodies

2019 ◽  
Author(s):  
Woonyung Hur ◽  
Marco Tarzia ◽  
Victoria E. Deneke ◽  
Esteban A. Terzo ◽  
Robert J. Duronio ◽  
...  
Keyword(s):  
Phase Separation ◽  
Gene Activation ◽  
Nuclear Body ◽  
Histone Mrnas ◽  
Histone Locus Bodies ◽  
Sex Combs ◽  
Zygotic Gene ◽  
Zygotic Gene Activation ◽  
And Function ◽  
Histone Locus

SummaryMany membrane-less organelles form through liquid-liquid phase separation, but how their size is controlled and whether size is linked to function remain poorly understood. The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of histone mRNAs. Here, we show that Drosophila HLBs form through phase separation of the scaffold protein multi-sex combs (Mxc). The size of HLBs is controlled in a precise and dynamic manner that is dependent on the cell cycle and zygotic gene activation. Control of HLB growth is achieved by a mechanism integrating nascent mRNAs at the histone locus, which catalyzes phase separation, and the nuclear concentration of Mxc, which is controlled by the activity of cyclin-dependent kinases. Reduced Cdk2 activity results in smaller HLBs and the appearance of nascent, misprocessed histone mRNAs. Our experiments thus identify a mechanism linking nuclear body growth and size with gene expression.

scholarly journals CDK-Regulated Phase Separation Seeded by Histone Genes Ensures Precise Growth and Function of Histone Locus Bodies

2020 ◽  
Vol 54 (3) ◽  
pp. 379-394.e6 ◽  
Author(s):  
Woonyung Hur ◽  
James P. Kemp ◽  
Marco Tarzia ◽  
Victoria E. Deneke ◽  
William F. Marzluff ◽  
...  
Keyword(s):  
Phase Separation ◽  
Histone Genes ◽  
Histone Locus Bodies ◽  
And Function ◽  
Histone Locus

scholarly journals Loss of Histone Locus Bodies in the Mature Hemocytes of Larval Lymph Gland Result in Hyperplasia of the Tissue in mxc Mutants of Drosophila

2020 ◽  
Vol 21 (5) ◽  
pp. 1586 ◽  
Author(s):  
Masanori Kurihara ◽  
Kouyou Komatsu ◽  
Rie Awane ◽  
Yoshihiro H. Inoue
Keyword(s):  
Ataxia Telangiectasia ◽  
Ectopic Expression ◽  
Mrna Levels ◽  
Lymph Glands ◽  
Histone Mrnas ◽  
Histone Locus Bodies ◽  
Responsible Gene ◽  
Sex Combs ◽  
Cycle Dependent ◽  
Histone Locus

Mutations in the multi sex combs (mxc) gene in Drosophila results in malignant hyperplasia in larval hematopoietic tissues, called lymph glands (LG). mxc encodes a component of the histone locus body (HLB) that is essential for cell cycle-dependent transcription and processing of histone mRNAs. The mammalian nuclear protein ataxia-telangiectasia (NPAT) gene, encoded by the responsible gene for ataxia telangiectasia, is a functional Mxc orthologue. However, their roles in tumorigenesis are unclear. Genetic analyses of the mxc mutants and larvae having LG-specific depletion revealed that a reduced activity of the gene resulted in the hyperplasia, which is caused by hyper-proliferation of immature LG cells. The depletion of mxc in mature hemocytes of the LG resulted in the hyperplasia. Furthermore, the inhibition of HLB formation was required for LG hyperplasia. In the mutant larvae, the total mRNA levels of the five canonical histones decreased, and abnormal forms of polyadenylated histone mRNAs, detected rarely in normal larvae, were generated. The ectopic expression of the polyadenylated mRNAs was sufficient for the reproduction of the hyperplasia. The loss of HLB function, especially 3′-end processing of histone mRNAs, is critical for malignant LG hyperplasia in this leukemia model in Drosophila. We propose that mxc is involved in the activation to induce adenosine deaminase-related growth factor A (Adgf-A), which suppresses immature cell proliferation in LG.

scholarly journals Minor zygotic gene activation is essential for mouse preimplantation development

2018 ◽  
Vol 115 (29) ◽  
pp. E6780-E6788 ◽  
Author(s):  
Ken-ichiro Abe ◽  
Satoshi Funaya ◽  
Dai Tsukioka ◽  
Machika Kawamura ◽  
Yutaka Suzuki ◽  
...  
Keyword(s):  
Dna Replication ◽  
Gene Activation ◽  
Marked Change ◽  
Cell Stage ◽  
Maternal Mrna ◽  
Maternal To Zygotic Transition ◽  
Before And After ◽  
H3k4me3 Mark ◽  
Zygotic Gene ◽  
Zygotic Gene Activation

In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.

scholarly journals Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion

2020 ◽  
Vol 21 (11) ◽  
pp. 4115 ◽  
Author(s):  
Isabel Gómez-Redondo ◽  
Priscila Ramos-Ibeas ◽  
Eva Pericuesta ◽  
Raúl Fernández-González ◽  
Ricardo Laguna-Barraza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alternative Splicing ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Gene Activation ◽  
Early Embryo ◽  
Early Embryo Development ◽  
Zygotic Gene ◽  
Zygotic Gene Activation ◽  
Induced Pluripotent

Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells.

scholarly journals Zygotic Gene Activation and Maternal Factors in Mammals

2007 ◽  
Vol 53 (4) ◽  
pp. 707-715 ◽  
Author(s):  
Naojiro MINAMI ◽  
Toru SUZUKI ◽  
Satoshi TSUKAMOTO
Keyword(s):  
Gene Activation ◽  
Maternal Factors ◽  
Zygotic Gene ◽  
Zygotic Gene Activation

scholarly journals Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development

EMBO Reports ◽  
2015 ◽  
Vol 16 (7) ◽  
pp. 803-812 ◽  
Author(s):  
Keisuke Aoshima ◽  
Erina Inoue ◽  
Hirofumi Sawa ◽  
Yuki Okada
Keyword(s):  
Embryonic Development ◽  
Gene Activation ◽  
H3k4 Methylation ◽  
Zygotic Gene ◽  
Zygotic Gene Activation ◽  
Early Mouse

scholarly journals DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence

2020 ◽  
Author(s):  
Amanda L. Fry ◽  
Amy Webster ◽  
Rojin Chitrakar ◽  
L. Ryan Baugh ◽  
E. Jane Albert Hubbard
Keyword(s):  
Cell Cycle ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Gene Activation ◽  
Dependent Manner ◽  
Germline Gene ◽  
C Elegans ◽  
Zygotic Gene ◽  
Zygotic Gene Activation

AbstractQuiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. In C. elegans mutant for daf-18, the sole C. elegans PTEN ortholog, primordial germ cells (PGCs) divide inappropriately in starvation conditions, in a TOR-dependent manner. Here, we further investigated the role of daf-18 in maintaining PGC quiescence. We found that maternal or zygotic daf-18 is sufficient to maintain cell cycle quiescence, that daf-18 acts in the germ line and soma, and that daf-18 affects timing of PGC divisions in fed animals. Importantly, our results also implicate daf-18 in zygotic germline gene activation, though not in germline fate specification. However, TOR is less important to zygotic germline gene expression, suggesting that in the absence of food daf-18/PTEN prevents inappropriate germline zygotic gene activation and cell division by distinct mechanisms.

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