ZNF445 is a primary regulator of genomic imprinting

Takahashi, Nozomi; Coluccio, Andrea; Thorball, Christian W.; Planet, Evarist; Shi, Hui; Offner, Sandra; Turelli, Priscilla; Imbeault, Michaël; Ferguson-Smith, Anne C.; Trono, Didier

doi:10.1101/gad.320069.118

Cited by 153 publications

(152 citation statements)

References 30 publications

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“…We further documented the genomic recruitment of the 16 KZFPs interacting with 3 or more unique preys, completing a previously established dataset (Imbeault et al , ) with additional ChIP‐seq studies (Table EV3). A majority was found at TEs or gene transcription start sites (TSS) (Fig D), but some were rather associated with other entities such as imprinting control regions (ICRs) for ZNF445 (Takahashi et al , ) and CTCF binding sites for ZNF764. In addition, few or no ChIP‐seq peaks were detected for ZNF446, ZNF546, ZNF213, and ZNF597, indicating different modalities or absence of DNA binding.…”

Section: Resultsmentioning

confidence: 99%

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

et al. 2019

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Krüppel‐associated box (KRAB)‐containing zinc finger proteins (KZFPs) are encoded in the hundreds by the genomes of higher vertebrates, and many act with the heterochromatin‐inducing KAP1 as repressors of transposable elements (TEs) during early embryogenesis. Yet, their widespread expression in adult tissues and enrichment at other genetic loci indicate additional roles. Here, we characterized the protein interactome of 101 of the ~350 human KZFPs. Consistent with their targeting of TEs, most KZFPs conserved up to placental mammals essentially recruit KAP1 and associated effectors. In contrast, a subset of more ancient KZFPs rather interacts with factors related to functions such as genome architecture or RNA processing. Nevertheless, KZFPs from coelacanth, our most distant KZFP‐encoding relative, bind the cognate KAP1. These results support a hypothetical model whereby KZFPs first emerged as TE‐controlling repressors, were continuously renewed by turnover of their hosts’ TE loads, and occasionally produced derivatives that escaped this evolutionary flushing by development and exaptation of novel functions.

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Section: Resultsmentioning

confidence: 99%

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

et al. 2019

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“…S12). KRAZ1 encodes a protein with Krüppel-type zinc finger structural motif also found in ZNF57, KRAZ2, and ZNF445; references [42][43][44]. As ZNF57, both KRAZ1 and KRAZ2 interacts with KAP1 [43].…”

Section: Density Peaks Revealed the Known Icr/gdmr Of Igf2r -Airn Impmentioning

confidence: 99%

“…The position of a candidate ICR for a gene (KRAZ1) in a chromosomal section with several ZFP genes. KRAZ1 encodes a factor with Krüppel-type zinc finger structural motif [42][43][44]. As ZNF57, KRAZ1 interacts with KAP1/TRIM28 [43].…”

Section: Supplemental Figuresmentioning

confidence: 99%

Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

Bina

Wyss

2019

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In mammals, parent-of-origin-specific gene expression is regulated by specific genomic DNA segments known as Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). In the mouse genome, the known ICRs/gDMRs often include clusters of a set of composite-DNA-elements known as ZFBS-morph overlaps. These elements consist of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. To improve detection of such clusters, we created density-plots. In genome-wide analyses, peaks in these plots pinpointed ~90% of the known ICRs/gDMRs and located candidate ICRs within relatively long genomic DNA sections. In several cases, the candidate ICRs mapped to chromatin boundaries, to a subset of gene-transcripts, or to both. By viewing the plots at the UCSC genome browser, we could examine the candidate ICRs in the context of the genes in their vicinity. This strategy uncovered several potential imprinted genes with a broad range of physiologically important functions. Examples include: folliculogenesis; lineage commitment of murine embryonic stem cells; the development of the junctional zone of the placenta; left-right patterning of the body axis; the development of the neocortex, hippocampus, and cerebellum; postnatal vision; self-renewal of mouse spermatogonial stem cells; and histone-to-protamine replacement during spermatogenesis. Predicted imprinted genes: Arid1b,

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“…The mouse remains the favourite animal model for studying the underlying mechanisms of imprinting regulation (reviewed in (1)). For example, the use of mouse models allowed the identification of ZFP57 and ZFP445 KRAB zinc-finger proteins as fundamental protection factors of methylation imprints at critical developmental stages (51,52). Therefore, inspection of methylation remains highly relevant for murine imprinted regions.…”

Section: Discussionmentioning

confidence: 99%

IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions

Klobučar

Kreibich

Krueger

et al. 2020

Preprint

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Genomic imprinting is an epigenetic phenomenon leading to parental allele-specific expression. Dosage of imprinted genes is crucial for normal development and its dysregulation accounts for several human disorders. This unusual expression pattern is mostly dictated by differences in DNA methylation between parental alleles at specific regulatory elements known as imprinting control regions (ICRs). Although several approaches can be used for methylation inspection, we lack an easy and cost-effective method to simultaneously measure DNA methylation at multiple imprinted regions. Here, we present IMPLICON, a new high-throughput method measuring DNA methylation levels at imprinted regions with base-pair resolution and over 1000-fold coverage. We initially designed IMPLICON to look at ICRs in adult tissues of inbred mice. Then, we validated it in hybrid mice from reciprocal crosses for which we could discriminate methylation profiles in the two parental alleles.Lastly, we developed a human version of IMPLICON and detected imprinting errors in embryonic and induced pluripotent stem cells. We also provide rules and guidelines to adapt this method for investigating the DNA methylation landscape of any set of genomic regions.In summary, IMPLICON is a rapid, cost-effective and scalable method, which could become the gold standard in both imprinting research and diagnostics.(OMIM#105830) syndromes caused by defects in the paternal or maternal chr15q11-q13 region, respectively (13,14).Most imprinted genes are located in clusters throughout the genome, containing a cisacting CpG-rich DNA element referred to as imprinting control region (ICR) (reviewed in (1)). The ICR is epigenetically marked by DNA methylation in a parent-of-origin fashion, which correlates with expression and/or silencing of the surrounding imprinted genes.Deletions of ICRs result in the loss of parental allele-specific expression within an imprinted cluster (15,16). ICRs acquire parental-specific DNA methylation in the germline, which are maintained throughout development and adulthood, resisting the global wave of demethylation and de novo methylation steps during early embryonic development (reviewed in (1,17,18)). The preservation of parental allele-specific methylation at ICRs, also known as germline differentially methylated regions (gDMRs), is fundamental for the correct maintenance of imprinted expression throughout life.Despite their importance, there is currently no robust, cost-effective and highthroughput method to assess the methylation status of ICRs across multiple imprinted regions (Suppl . Table 1; reviewed in (19)). The traditional way of measuring DNA methylation is bisulfite sequencing (20). Bisulfite treatment of DNA results in deamination of unmodified cytosines to uracils, whereas methylated cytosines remain unchanged. This is followed by PCR amplification of a region of interest followed by subcloning and Sanger sequencing. This method is laborious and not cost-effective for multiple samples or viewpoints. Alternatively, bisulfite ...

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ZNF445 is a primary regulator of genomic imprinting

Cited by 153 publications

References 30 publications

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification

Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome

IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions

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