scholarly journals Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition

Cell Reports ◽  
2020 ◽  
Vol 31 (12) ◽  
pp. 107783 ◽  
Author(s):  
Wen Xi Cao ◽  
Sarah Kabelitz ◽  
Meera Gupta ◽  
Eyan Yeung ◽  
Sichun Lin ◽  
...  
Keyword(s):  
Transcriptional Repressors ◽  
Temporal Regulation ◽  
Maternal To Zygotic Transition

scholarly journals Precise temporal regulation of post-transcriptional repressors is required for an orderly Drosophila maternal-to-zygotic transition

2019 ◽  
Author(s):  
Wen Xi Cao ◽  
Sarah Kabelitz ◽  
Meera Gupta ◽  
Eyan Yeung ◽  
Sichun Lin ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Gene Products ◽  
Transcriptional Repressors ◽  
Protein Coding ◽  
Temporal Regulation ◽  
Maternal Contribution ◽  
Maternal To Zygotic Transition ◽  
Zygotic Gene ◽  
Ubiquitin Proteasome ◽  
Coding Capacity

SUMMARYIn animal embryos the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents over half of the protein coding capacity of the Drosophila melanogaster genome and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). While the ubiquitin-proteasome system is necessary for clearance of all four repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL and ME31B for degradation early in the MZT; the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG makes the protein immune to degradation. We show that artificially persistent SMG downregulates the zygotic re-expression of mRNAs whose maternal contribution is cleared by SMG. Thus, clearance of SMG permits an orderly MZT.

Phosphotyrosine-Dependent Signaling: the Role of CoREST/REST Transcriptional Repressors in Neuroblastoma

2017 ◽  
Author(s):  
TL Vu-Han ◽  
S Buhs ◽  
H Gerull ◽  
M Horstmann ◽  
P Nollau
Keyword(s):  
Transcriptional Repressors

Two-Step Maternal-to-Zygotic Transition with Two-Phases of Parental Genome Contributions

2018 ◽  
Author(s):  
Peng Zhao ◽  
Xuemei Zhou ◽  
Kun Shen ◽  
Zhenzhen Liu ◽  
Tianhe Cheng ◽  
...  
Keyword(s):  
Parental Genome ◽  
Maternal To Zygotic Transition ◽  
Two Phases

scholarly journals CD14+ monocytes repress gamma globin expression at early stages of erythropoiesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven Heshusius ◽  
Esther Heideveld ◽  
Marieke von Lindern ◽  
Emile van den Akker
Keyword(s):  
Mononuclear Cells ◽  
Therapeutic Option ◽  
Globin Genes ◽  
Beta Globin ◽  
Hematopoietic Progenitors ◽  
Peripheral Blood Mononuclear ◽  
Temporal Regulation ◽  
Gamma Globin ◽  
Cd34 Cells ◽  
Adult Hemoglobin

AbstractIn β-hemoglobinopathies, reactivation of gamma- at the expense of beta-globin is a prominent therapeutic option. Expression of the globin genes is not strictly intrinsically regulated during erythropoiesis, supported by the observation that fetal erythroid cells switch to adult hemoglobin expression when injected in mice. We show cultured erythroblasts are a mix of HbA restrictive and HbA/HbF expressing cells and that the proportion of cells in the latter population depends on the starting material. Cultures started from CD34+ cells contain more HbA/HbF expressing cells compared to erythroblasts cultured from total peripheral blood mononuclear cells (PBMC). Depletion of CD14+ cells from PBMC resulted in higher HbF/HbA percentages. Conversely, CD34+ co-culture with CD14+ cells reduced the HbF/HbA population through cell–cell proximity, indicating that CD14+ actively repressed HbF expression in adult erythroid cultures. RNA-sequencing showed that HbA and HbA/HbF populations contain a limited number of differentially expressed genes, aside from HBG1/2. Co-culture of CD14+ cells with sorted uncommitted hematopoietic progenitors and CD34-CD36+ erythroblasts showed that hematopoietic progenitors prior to the hemoglobinized erythroid stages are more readily influenced by CD14+ cells to downregulate expression of HBG1/2, suggesting temporal regulation of these genes. This possibly provides a novel therapeutic avenue to develop β-hemoglobinopathies treatments.

scholarly journals STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

2021 ◽  
Vol 22 (1) ◽  
pp. 460
Author(s):  
Huan Ou-Yang ◽  
Shinn-Chih Wu ◽  
Li-Ying Sung ◽  
Shiao-Hsuan Yang ◽  
Shang-Hsun Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Fluorescent Protein ◽  
Mouse Embryos ◽  
Cell Nuclei ◽  
Cell Stage ◽  
Promoter Assay ◽  
Maternal To Zygotic Transition ◽  
Mouse Zygotes ◽  
Time Specific

The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse zygotes to the two-cell stage. Our previous study reported that mouse granzyme g (Gzmg), a serine-type protease, is required for the MZT. In this study, we further identified the maternal factors that regulate the Gzmg promoter activity in the zygote to the two-cell stage of mouse embryos. A full-length Gzmg promoter from mouse genomic DNA, FL-pGzmg (−1696~+28 nt), was cloned, and four deletion constructs of this Gzmg promoter, Δ1-pGzmg (−1369~+28 nt), Δ2-pGzmg (−939~+28 nt), Δ3-pGzmg (−711~+28 nt) and Δ4-pGzmg (−417~+28 nt), were subsequently generated. Different-sized Gzmg promoters were used to perform promoter assays of mouse zygotes and two-cell stage embryos. The results showed that Δ4-pGzmg promoted the highest expression level of the enhanced green fluorescent protein (EGFP) reporter in the zygotes and two-cell embryos. The data suggested that time-specific transcription factors upregulated Gzmg by binding cis-elements in the −417~+28-nt Gzmg promoter region. According to the results of the promoter assay, the transcription factor binding sites were predicted and analyzed with the JASPAR database, and two transcription factors, signal transducer and activator of transcription 3 (STAT3) and GA-binding protein alpha (GABPα), were identified. Furthermore, STAT3 and GABPα are expressed and located in zygote pronuclei and two-cell nuclei were confirmed by immunofluorescence staining; however, only STAT3 was recruited to the mouse zygote pronuclei and two-cell nuclei injected with the Δ4-pGzmg reporter construct. These data indicated that STAT3 is a maternal transcription factor and may upregulate Gzmg to promote the MZT. Furthermore, treatment with a STAT3 inhibitor, S3I-201, caused mouse embryonic arrest at the zygote and two-cell stages. These results suggest that STAT3, a maternal protein, is a critical transcription factor and regulates Gzmg transcription activity in preimplantation mouse embryos. It plays an important role in the maternal-to-zygotic transition during early embryonic development.

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