A nuclear licence to silence transposons

Gould, Poppy A.; Rowe, Helen M.

doi:10.15252/embr.201949262

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Recently, the location of SETDB1 inside the nucleus was discovered to be mediated by ATF7IP, which increases the ubiquitination of SETDB1 to promote its enzymatic activity [ 84 , 85 , 86 ]. The fibronectin type-III (FNIII) domain of ATF7IP plays a certain role in the transcriptional repression function mediated by the SETDB1-ATF7IP complex.…”

Section: Biological Functions Of Setdb1mentioning

confidence: 99%

The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma

Sun

et al. 2021

IJMS

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SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling. Therefore, aberrant trimethylation at H3K9 due to amplification, mutation or deletion of SETDB1 may lead to transcriptional repression of various tumour-suppressing genes and other related genes in cancer cells. Lung cancer is the most common type of cancer worldwide in which SETDB1 amplification and H3K9 hypermethylation have been indicated as potential tumourigenesis markers. In contrast, frequent inactivation mutations of SETDB1 have been revealed in mesothelioma, an asbestos-associated, locally aggressive, highly lethal, and notoriously chemotherapy-resistant cancer. Above all, the different statuses of SETDB1 indicate that it may have different biological functions and be a potential diagnostic biomarker and therapeutic target in lung cancer and mesothelioma.

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Section: Biological Functions Of Setdb1mentioning

confidence: 99%

The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma

Sun

et al. 2021

IJMS

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“…4C). SETDB1 is targeted for proteasomal degradation unless it is retained in the nucleus ( 33 , 34 ) where it is monoubiquitinated, which is essential to its function ( 35 , 36 ). We hypothesized that a ZFP819-TRIM28 complex might contribute to nuclear retention of SETDB1 levels, and we validated that ZFP819 interacts with TRIM28 by coimmunoprecipitation (Fig.…”

Section: Resultsmentioning

confidence: 99%

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819

et al. 2022

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Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)–like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across Zscan4 , to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes.

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A nuclear licence to silence transposons

Cited by 2 publications

References 13 publications

The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma

The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819

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