G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis

Olsen, Jonathan B.; Wong, Leo; Deimling, Steven; Miles, Amanda; Guo, Hongbo; Li, Yue; Zhang, Zhaolei; Greenblatt, Jack; Emili, Andrew; Tropepe, Vincent

doi:10.1016/j.stemcr.2016.06.012

Cited by 25 publications

(26 citation statements)

References 53 publications

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“…zNCK2B knockdown and rescued embryos were assayed at 48 hpf (hours post fertilization) for midbrain GFP expression in the zebrafish enhancer trap line SAGFF(LF)223A, where GFP was inserted adjacent to lhx9 140 . Wild-type AB embryos were similarly injected with zNCK2B or control morpholino and mRNA, fixed at 48 hpf and assayed by whole mount in situ hybridization for lef1 expression as previously described 141 .…”

Section: Nck2 Function In Zebrafishmentioning

confidence: 99%

A reference map of the human protein interactome

Luck

Kim

Lambourne

et al. 2019

Preprint

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Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human "all-by-all" binary reference interactome map, or "HuRI". With ~53,000 highquality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.

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Section: Nck2 Function In Zebrafishmentioning

confidence: 99%

A reference map of the human protein interactome

Luck

Kim

Lambourne

et al. 2019

Preprint

Self Cite

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“…The patterns of H3K9me1 or H3K9me2 are different during development, as there are either more mono-or dimethylations at H3K9 during the maturation of the auditory system (49). During the development of the zebrafish retina, EHMT2 expression and H3K9me2 markers have been noted to be closely associated (50). H3K9 methylation is a crucial event in reprogramming to pluripotency (51).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of EHMT2 associated with H3K9me2 level contributes to the poor prognosis of gastric cancer

et al. 2020

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Di-methylated lysine 9 of histone H3 (H3K9me2), regulated by histone methyltransferases, is involved in the epigenetic regulation of tumor-associated genes. The present study aimed to evaluate whether the H3K9me2 methylation level is associated with the expression level of euchromatic histone lysine methyltransferase 2 (EHMT2) in the prognosis of gastric cancer (GC). H3K9me2 methylation level and EHMT2 expression level were detected by immunohistochemistry in 118 GC samples. The clinicopathological significance of H3K9me2 and EHMT2 in patients with GC was assessed using a paired Student's t-test, χ 2 test, Kaplan-Meier analysis with a log-rank test and Cox's proportional hazard analysis. Strong positive immunostaining of H3K9me2 and EHMT2 was observed in cancerous tissues compared with adjacent non-cancerous tissues. Positive immunostaining of EHMT2 and H3K9me2 was associated with lymph node metastasis, pathological grade and tumor-node-metastasis stage. H3K9me2 expression level was increased in tumor tissue and associated with worse specific-disease and disease-free survival time. In addition, EHMT2 protein expression levels were associated with the expression levels of H3K9me2. Low expression levels of H3K9me2 and EHMT2 predicted a better prognosis of patients with GC. The survival time of patients with a high expression of H3K9me2 and/or EHMT2 was significantly shorter compared with that of the patients with a low expression of H3K9me2 and/or EHMT2. In conclusion, an overexpression pattern of H3K9me2 and/or EHMT2 may be associated with clinicopathological features of GC and may be predictor markers of progression and prognosis in patients with GC, in addition to putative therapeutic targets.

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“…No Zfp644 -deficient mouse model has been generated so far, and only a fish model deficient for ZNF644 was previously described [22]. To investigate the molecular mechanism of ZNF644 , Olsen et al [22] prepared two different morphant models (MO) of znf644 , based on two znf644 isoforms (a and b) whose phenotype was severe and included changes in developing retina, midbrain, and eye size. Both znf644a-MO and znf644b-MO showed signs of microphthalmia and disrupted midbrain morphology.…”

Section: Discussionmentioning

confidence: 99%

“…Knockdown of ZNF644 in a cell culture results in reduced cell proliferation and higher sensitivity to replication stress as well as an increase of DNA damage in replicating cells [21]. Studies in fish showed that ZNF644 with G9a/GLP complex are responsible for histone methylation critical for gene silencing during neuronal differentiation in retinal neuron differentiation [22].…”

Section: Introductionmentioning

confidence: 99%

Myopia disease mouse models: a missense point mutation (S673G) and a protein-truncating mutation of the Zfp644 mimic human disease phenotype

et al. 2019

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Zinc finger 644 (Zfp644 in mouse, ZNF644 in human) gene is a transcription factor whose mutation S672G is considered a potential genetic factor of inherited high myopia. ZNF644 interacts with G9a/GLP complex, which functions as a H3K9 methyltransferase to silence transcription. In this study, we generated mouse models to unravel the mechanisms leading to symptoms associated with high myopia. Employing TALEN technology, two mice mutants were generated, either with the disease-carrying mutation ( Zfp644 S673G ) or with a truncated form of Zfp644 ( Zfp644 Δ8 ). Eye morphology and visual functions were analysed in both mutants, revealing a significant difference in a vitreous chamber depth and lens diameter, however the physiological function of retina was preserved as found under the high-myopia conditions. Our findings prove that ZNF644/Zfp644 is involved in the development of high-myopia, indicating that mutations such as, Zfp644 S673G and Zfp644 Δ8 are causative for changes connected with the disease. The developed models represent a valuable tool to investigate the molecular basis of myopia pathogenesis and its potential treatment. Electronic supplementary material The online version of this article (10.1186/s13578-019-0280-4) contains supplementary material, which is available to authorized users.

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G9a and ZNF644 Physically Associate to Suppress Progenitor Gene Expression during Neurogenesis

Cited by 25 publications

References 53 publications

A reference map of the human protein interactome

A reference map of the human protein interactome

Increased expression of EHMT2 associated with H3K9me2 level contributes to the poor prognosis of gastric cancer

Myopia disease mouse models: a missense point mutation (S673G) and a protein-truncating mutation of the Zfp644 mimic human disease phenotype

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