scholarly journals The role of ZFP57 and additional KRAB-zinc finger proteins in the maintenance of human imprinted methylation and multi-locus imprinting disturbances

2020 ◽  
Vol 48 (20) ◽  
pp. 11394-11407
Author(s):  
Ana Monteagudo-Sánchez ◽  
Jose Ramon Hernandez Mora ◽  
Carlos Simon ◽  
Adam Burton ◽  
Jair Tenorio ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Expression Profiling ◽  
Zinc Finger Proteins ◽  
Early Embryogenesis ◽  
Mouse Embryos ◽  
Parental Origin ◽  
Embryonic Genome ◽  
Repressor Complex ◽  
Genome Activation

Abstract Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation that is resistant to embryonic reprogramming, resulting in parental origin-specific monoallelic gene expression. A subset of individuals affected by imprinting disorders (IDs) displays multi-locus imprinting disturbances (MLID), which may result from aberrant establishment of imprinted differentially methylated regions (DMRs) in gametes or their maintenance in early embryogenesis. Here we investigated the extent of MLID in a family harbouring a ZFP57 truncating variant and characterize the interactions between human ZFP57 and the KAP1 co-repressor complex. By ectopically targeting ZFP57 to reprogrammed loci in mouse embryos using a dCas9 approach, we confirm that ZFP57 recruitment is sufficient to protect oocyte-derived methylation from reprogramming. Expression profiling in human pre-implantation embryos and oocytes reveals that unlike in mice, ZFP57 is only expressed following embryonic-genome activation, implying that other KRAB-zinc finger proteins (KZNFs) recruit KAP1 prior to blastocyst formation. Furthermore, we uncover ZNF202 and ZNF445 as additional KZNFs likely to recruit KAP1 to imprinted loci during reprogramming in the absence of ZFP57. Together, these data confirm the perplexing link between KZFPs and imprint maintenance and highlight the differences between mouse and humans in this respect.

scholarly journals Erratum: Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins

2009 ◽  
Vol 27 (5) ◽  
pp. 485-485
Author(s):  
Subhashini Chandrasekharan ◽  
Sapna Kumar ◽  
Cory M Valley ◽  
Arti Rai
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Proteins ◽  
Open Science

The role of RNA-polymerase II transcription in embryonic nucleologenesis by bovine embryos

Biologia ◽  
2010 ◽  
Vol 65 (3) ◽  
Author(s):  
Mária Kovalská ◽  
Ida Petrovičová ◽  
František Strejček ◽  
Marian Adamkov ◽  
Erika Halašová ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
De Novo ◽  
Control Group ◽  
Bovine Embryos ◽  
Embryonic Genome Activation ◽  
Embryonic Genome ◽  
Autoradiographic Labeling ◽  
Genome Activation

AbstractThe early stages of embryonic development are maternally driven. As development proceeds, maternally inherited informational molecules decay, and embryogenesis becomes dependent on de novo synthesized RNAs of embryonic genome. The aim of the present study is to investigate the role of de novo transcription in the development of embryos during embryonic genome activation. Autoradiography for detection of transcriptional activity and transmission electron microscopy were applied in in vitro produced bovine embryos cultured to the late 8-cell stage with or without (control group) α-amanitin, specific inhibitor of RNA-polymerases II and III transcription. The α-amanitin (AA) groups presented three sets of embryos cultivated with AA in different time intervals (6, 9 and 12 h). In control group, nucleoplasm and nucleolar structures displayed strong autoradiographic labeling and showed initial development of fibrillo-granular nucleoli. In α-amanitin groups, lack of autoradiographic labeling and disintegrated nucleolus precursor bodies (NPBs) stage were observed. Inhibition of RNA polymerase II (RNA pol II) already in the early phases of embryonic genome activation has detrimental effect on nucleolar formation and embryo survival, what was shown for the first time.

The Regulation of Zinc Finger Proteins by Mirnas Enriched in ALL-Microvesicles

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1448-1448
Author(s):  
Huiyu Li ◽  
Xiaomei Chen ◽  
Wei Xiong ◽  
Fang Liu ◽  
Shiang Huang
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Expression Profiles ◽  
Zinc Fingers ◽  
Zinc Finger Proteins ◽  
Bioactive Molecules ◽  
Chromosomal Protein ◽  
Normal Peripheral Blood ◽  
Finger Protein

Abstract Abstract 1448 Microvesicles (MVs) are submicrometric membrane fragments and they can “hijack” membrane components and engulf cytoplasmic contents from their cellular origin. MVs are enriched in various bioactive molecules of their parental cells, such as proteins, DNA, mRNA and miRNAs. Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA (miRNA) between cells. MVs miRNAs may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. We determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. We identified 182 and 166 dysregulated miRNAs in MVs derived from Nalm 6 cells and from Jurkat cells, respectively. Both up regulated (123/182 in Nalm 6-MVs and 114/166 in Jurkat- MVs) and down regulated (59/182 in Nalm 6-MVs and 52/166 in Jurkat- MVs) expressions were observed compared with MVs from normal peripheral blood the MVs normal control. When we analyzed those miRNA with bioinformatic tools (TargetScan), we found an interesting phenomenon that presence of 111 zinc fingers genes were regulated by 52 miRNAs, indicating that the ALL-microvesicles were enriched with miRNAs regulating zinc finger proteins. They encompassed zinc fingers and homeoboxes 2, zinc finger, ZZ-type containing 3, zinc finger, SWIM-type containing 1, zinc finger, RAN-binding domain containing 3, zinc finger, NFX1-type containing 1, zinc finger, MYM-type 4, zinc finger, FYVE domain containing 1 and their 5 subtypes; zinc finger, DHHC-type containing16, and other subtypes; zinc finger, CCHC domain containing 14 and 7A, zinc finger, BED-type containing 4; zinc finger protein, X-linked; zinc finger protein, multitype 2; zinc finger protein 81, and their 55 subtypes; zinc finger and SCAN domain containing 18, zinc finger and BTB domain containing 9. ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. This provides clues that genes commonly function together. It is worth noting that 52 miRNA regulating above zinc finger protein genes were up-expressed, suggeting that miRNA regulating zinc fingers were active in ALL-MVs. Zinc finger proteins are important transcriptions in eukaryotes and play roles in regulating gene. Some members of the Zinc finger family have close relationaship with tumour. Zinc finger X-chromosomal protein (Zfx) is a protein that in humans is encoded by the ZFX gene. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, gastric tumoural tissues, and leukemia. [1,2]. Zinc finger and homeoboxes 2 (ZHX2) was target gene of miRNA-1260. The role of miRNA are negatively regulated host gene expressions. ZHX2 inhibits HCC cell proliferation by preventing expression of Cyclins A and E, and reduces growth of xenograft tumors. Loss of nuclear ZHX2 might be an early step in the development of HCC[3]. In our study, the miRNA-1260 were 9 fold higher in ALL MVs. In leukeima microenvironment, ALL-MVs may transfer aberantly expressed miRNAs to their target cell lead to abnormally regulated the zinc finger proteins that may play roles in ALL. In this study, we demonstrated that ALL-microvesicles were enriched with expression changes of distinct sets of miRNAs regulating zinc finger proteins. Futhermore, Zinc fingers were active in ALL-MVs and commonly function together. Disclosures: No relevant conflicts of interest to declare.

The role of C2H2 zinc finger proteins in plant responses to abiotic stresses

2018 ◽  
Vol 165 (4) ◽  
pp. 690-700 ◽  
Author(s):  
Ke Wang ◽  
Yanfei Ding ◽  
Chong Cai ◽  
Zhixiang Chen ◽  
Cheng Zhu
Keyword(s):  
Zinc Finger ◽  
Abiotic Stresses ◽  
Zinc Finger Proteins ◽  
Plant Responses ◽  
C2h2 Zinc Finger

scholarly journals Tet enzymes are essential for early embryogenesis and completion of embryonic genome activation

EMBO Reports ◽  
2021 ◽  
Author(s):  
Julia Arand ◽  
H Rosaria Chiang ◽  
David Martin ◽  
Michael P Snyder ◽  
Julien Sage ◽  
...  
Keyword(s):  
Early Embryogenesis ◽  
Embryonic Genome Activation ◽  
Embryonic Genome ◽  
Tet Enzymes ◽  
Genome Activation

scholarly journals Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins

2009 ◽  
Vol 27 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Subhashini Chandrasekharan ◽  
Sapna Kumar ◽  
Cory M Valley ◽  
Arti Rai
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Proteins ◽  
Open Science

scholarly journals Embryonic gene transcription in the spiny mouse (Acomys cahirinus): an investigtion into the embryonic genome activation

2018 ◽  
Author(s):  
Jared Mamrot ◽  
David K. Gardner ◽  
Peter Temple-Smith ◽  
Hayley Dickinson
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Gene Transcription ◽  
De Novo ◽  
Mouse Embryos ◽  
Spiny Mouse ◽  
Acomys Cahirinus ◽  
Embryonic Genome Activation ◽  
Embryonic Genome ◽  
Genome Activation

Our understanding of genetic mechanisms driving early embryonic development is primarily based on experiments conducted on mice, however translation of findings can be limited by physiological differences between mice and humans. To address this, we investigated whether the spiny mouse (Acomys cahirinus) is a closer model of early human embryonic development due to their more human-like endocrine profile. We therefore characterised the initiation of gene transcription in the spiny mouse embryo and compared the pattern of gene expression during the embryonic genome activation (EGA) with common mouse and human embryos. Naturally-mated spiny mouse embryos were obtained at the 2-cell, 4-cell and 8-cell stages of development (n=4 biological replicates per stage). RNA-Seq of these samples produced 709.1M paired-end reads in total. De novo assembly of reads was conducted using Trinity. Embryo-specific transcripts were extracted from the de novo assembly and added to the reference spiny mouse transcriptome. Transcription was first detected between the 2-cell and 4-cell stages for the majority of genes (n=3,428), with fewer genes first transcribed between the 4-cell and 8-cell stages (n=1,150). The pattern of gene expression in spiny mouse embryos during this period of development is more human-like than common mouse embryos. This is the first evidence the spiny mouse may provide a more suitable model of human embryonic development. The improved reference Acomys cahirinus transcriptome is publically accessible, further increasing the value of this tool for ongoing research. Further investigation into early development in the spiny mouse is warranted.

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