The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes

Ding, Dong; Bergmaier, Philipp; Sachs, Parysatis; Klangwart, Marius; Rückert, Tamina; Bartels, Nora; Demmers, Jeroen; Dekker, Mike R.; Poot, Raymond A.; Mermoud, Jacqueline E.

doi:10.1074/jbc.ra117.000959

Cited by 31 publications

(73 citation statements)

References 59 publications

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“…It has been confirmed in previous studies that SMARCAD1 and its orthologs mainly function by altering the structure of chromatin (Awad et al, 2010;Byeon et al, 2013;Steglich et al, 2015;Lee et al, 2017). They can not only regulate gene expression by promoting dissociation of nucleosomes, but also make an important contribution to gene silencing of centromeres, telomeres, and other regions (Neves-Costa et al, 2009;Rowbotham et al, 2011;Yu et al, 2011;Durand-Dubief et al, 2012;Steglich et al, 2015;Lee et al, 2017;Ding et al, 2018;Jahn et al, 2018). SMARCAD1 and its orthologs mediated gene silencing is mainly achieved by maintaining heterochromatin markers on nucleosomes (Durand-Dubief et al, 2012;Taneja et al, 2017;Sachs et al, 2019) or recruiting the methyltransferase G9a to modify newly synthesized histones (such as H3K9me3) for establishing heterochromatin de novo during DNA replication (Rowbotham et al, 2011;Yu et al, 2011).…”

Section: The Domain Architectures and Biological Functions Of Smarcadmentioning

confidence: 68%

“…Different from the role of SMARCAD1 in transcription activation, it is surprising and interesting that SMARCAD1 and all of its orthologs can localize heterochromatin and contribute to the establishment and maintenance of heterochromatin (Neves-Costa et al, 2009;Rowbotham et al, 2011;Stralfors et al, 2011;Yu et al, 2011;Durand-Dubief et al, 2012;Steglich et al, 2015;Taneja et al, 2017;Ding et al, 2018;Jahn et al, 2018;Sachs et al, 2019). Rowbotham et al (2011) used FLAG-affinity protein purification in HEK293 cells to identify the interaction partners of SMARCAD1.…”

Section: Smarcad1 Fun30 Establishes and Maintains The Heterochromatinmentioning

confidence: 99%

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The Mechanism of Chromatin Remodeler SMARCAD1/Fun30 in Response to DNA Damage

Tong

2020

Front. Cell Dev. Biol.

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DNA packs into highly condensed chromatin to organize the genome in eukaryotes but occludes many regulatory DNA elements. Access to DNA within nucleosomes is therefore required for a variety of biological processes in cells including transcription, replication, and DNA repair. To cope with this problem, cells employ a set of specialized ATP-dependent chromatin-remodeling protein complexes to enable dynamic access to packaged DNA. In the present review, we summarize the recent advances in the functional and mechanistic studies on a particular chromatin remodeler SMARCAD1 Fun30 which has been demonstrated to play a key role in distinct cellular processes and gained much attention in recent years. Focus is given to how SMARCAD1 Fun30 regulates various cellular processes through its chromatin remodeling activity, and especially the regulatory role of SMARCAD1 Fun30 in gene expression control, maintenance and establishment of heterochromatin, and DNA damage repair. Moreover, we review the studies on the molecular mechanism of SMARCAD1 Fun30 that promotes the DNA end-resection on double-strand break ends, including the mechanisms of recruitment, activity regulation and chromatin remodeling.

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Section: The Domain Architectures and Biological Functions Of Smarcadmentioning

confidence: 68%

Section: Smarcad1 Fun30 Establishes and Maintains The Heterochromatinmentioning

confidence: 99%

The Mechanism of Chromatin Remodeler SMARCAD1/Fun30 in Response to DNA Damage

Tong

2020

Front. Cell Dev. Biol.

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“…S8B). Moreover, KAP1 enrichment is specific for Xist promoter, as neither of the other regions known to be associated with KAP1 that we have tested, Znf629 and Ezr 66 , show an increased KAP1 association upon Rif1 deletion.…”

Section: Rif1 Negatively Regulates Kap1 Association With Xist Promotementioning

confidence: 79%

A RIF1/KAP1-based toggle switch stabilises the identities of the inactive and active X chromosomes during X inactivation

Enervald

Powell

Boteva

et al. 2020

Preprint

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Dosage compensation for the X chromosome-linked genes in female placental mammals is achieved through the random silencing of one of the two X chromosomes.The onset of random X inactivation in mouse embryos and in differentiating embryonic stem cells requires the switch from a symmetric state, where both X chromosomes are equivalent, to an asymmetric state, where the identity of the future inactive and active X chromosomes are assigned. This "choice", initiated by a stochastic event, needs to evolve into a stable and transmissible state. The transition from bi-to mono-allelic expression of the long non-coding RNA Tsix is thought to be one of the initial events breaking the symmetry of the two X chromosomes. Here we show that the asymmetric expression of Tsix triggers in turn the switch of RIF1 association with the Xist promoter from dynamic and symmetric to stable and asymmetric (on the future inactive X). On the future inactive X, RIF1 then plays an essential role in the upregulation of Xist, thus initiating the consolidation and stable transmission of the identity of the inactive X.Tsix-dependent exclusion of RIF1 from the future active X chromosome in turn permits the association of KAP1 with the Xist promoter, thus marking the future active X chromosome. Timely mono-allelic association of KAP1 is important for a stable choice and for X inactivation. We present here a double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1. This system coordinates the identification of the active and inactive X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.

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“…In addition to the widely recognized co-repressor function of TRIM28 for KRAB-ZNFs, TRIM28 can also interact with SMARCAD1 (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily A, containing DEAD/H box 1) through the CUE (coupling of ubiquitin conjugation to ER degradation) domain of SMARCAD1 (15,56). SMARCAD1 not only binds to and regulates TRIM28 target genes in embryonic stem cells but also appears to compete with KRAB-ZNFs for interaction with TRIM28 (15). Further investigation of both the distinct and overlapping roles of SMARCAD1-TRIM28 and KRAB-ZNFs-TRIM28 or KRAB-ZNFs-TRIM28-K304Q could illuminate their roles in gene speci city and modes of regulation.…”

Section: Discussionmentioning

confidence: 99%

“…), TRIM28 can be targeted to chromatin (13). TRIM28 can recruit chromatin writers and readers (DNMTs, SMARCAD1, and HP1s) (14)(15)(16). The scaffold function of TRIM28 is largely mediated by the intrinsically disordered regions (IDRs).…”

Section: Introductionmentioning

confidence: 99%

Mutation of TRIM28-Lys304 to Gln Attenuates its Interaction with KRAB-ZNFs and Promotes Differentiation of Erythroleukemic K562 Cells

Chang¹,

Lin²,

Kang³

et al. 2020

Preprint

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BackgroundTRIM28/KAP1/TIF1β is a key epigenetic modifier. Genetic ablation of trim28 is embryonic lethal although RNAi-mediated knockdown in somatic cells yields viable cells. Reduction in TRIM28 abundance at the cellular or organismal level results in polyphenism. Posttranslational modifications such as phosphorylation and sumoylation have been shown to regulate TRIM28 activity. Moreover, the methylation of DNA, RNA and histones and acetylation of histones are key epigenetic modifications that regulate gene expression. A number of lysine residues of TRIM28 are subject to acetylation, but how acetylation of TRIM28 affects its functions remains poorly understood. ResultsHere we report that, compared with wild-type TRIM28, the acetylation-mimic mutant TRIM28-K304Q has an altered interaction with Krüppel-associated box zinc-finger proteins (KRAB-ZNFs), with consequent effects on the phenotype of the erythroleukemic cell line K562. TRIM28-K304Q was comparable with its wild-type counterpart with respect to intracellular level, homodimerization, phosphorylation at S473 and S824, and interactions with heterochromatin-binding protein HP1. The expression of embryonic-related and fetal globin genes was activated in TRIM28-K304Q mutant cells. Transcriptome analysis revealed that TRIM28-K304Q and TRIM28 knockout K562 cells had similar global gene expression profiles, yet the profiles differed considerably from that of wild-type K562 cells. The gene expression ensemble of mutant K562 cells indicated a general induction of differentiation-promoting genes and attenuation of proliferation-promoting genes. ConclusionsThese results suggest that acetylation/deacetylation of K304 in TRIM28 or TRIM28-K304Q constitutes a switch for regulating its interaction with KRAB-ZNFs and alters the gene regulation of this key epigenetic modifier as demonstrated by the acetylation mimic TRIM28-K304Q.

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The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes

Cited by 31 publications

References 59 publications

The Mechanism of Chromatin Remodeler SMARCAD1/Fun30 in Response to DNA Damage

The Mechanism of Chromatin Remodeler SMARCAD1/Fun30 in Response to DNA Damage

A RIF1/KAP1-based toggle switch stabilises the identities of the inactive and active X chromosomes during X inactivation

Mutation of TRIM28-Lys304 to Gln Attenuates its Interaction with KRAB-ZNFs and Promotes Differentiation of Erythroleukemic K562 Cells

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