CTCF participates in DNA damage response via poly(ADP-ribosyl)ation

Han, Deqiang; Chen, Qian; Shi, Jiazhong; Zhang, Feng; Yu, Xiaochun

doi:10.1038/srep43530

Cited by 27 publications

(38 citation statements)

References 40 publications

(62 reference statements)

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“…12 Recent evidence shows that CTCF participates in the DNA damage response via PARylation, and CTCF-deficient cells are hypersensitive to genotoxic stress. 14 In this study, we demonstrate that PARP1-mediated PARylation is pivotal for maintaining the functions of CTCF in repressing transcription of target genes in NB cells. As an inhibitor of PARP1-mediated PARylation of CTCF, FOXD3-AS1 is potentially involved in regulating DNA damage repair and increasing sensitivity to chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 60%

“…Stable knockdown of FOXD3-AS1 facilitated the anchorage-independent growth of NB cells ( Figure 6A). Since PARP1 and CTCF are involved in the repair of DNA damage, 13,14 the roles of FOXD3-AS1 in this process were further investigated. Western blot and flow cytometry assays showed that knockdown of PARP1 or CTCF led to increased levels of phosphorylated H2AX (gH2AX) and RAD51 ( Figure S8A), markers for DNA damage and homologous recombination repair, and facilitated the cisplatin-induced DNA damage and apoptosis in NB cells ( Figures S8A and S8B).…”

Section: Foxd3-as1 Harbors Tumor-suppressive Properties By Repressingmentioning

confidence: 99%

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RETRACTED: Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF

Zhao

Huang

et al. 2018

Molecular Therapy

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Neuroblastoma (NB) is the most common extracranial tumor in childhood. Recent studies have implicated the emerging roles of long noncoding RNAs (lncRNAs) in tumorigenesis and aggressiveness. However, the functions and targets of risk-associated lncRNAs in NB progression still remain to be determined. Herein, through mining of public microarray datasets, we identify lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) as an independent prognostic marker for favorable outcome of NB patients. FOXD3-AS1 is downregulated in NB tissues and cell lines, and ectopic expression of FOXD3-AS1 induces neuronal differentiation and decreases the aggressiveness of NB cells in vitro and in vivo. Mechanistically, as a nuclear lncRNA, FOXD3-AS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1) to inhibit the poly(ADP-ribosyl)ation and activation of CCCTC-binding factor (CTCF), resulting in derepressed expression of downstream tumor-suppressive genes. Rescue experiments indicate that FOXD3-AS1 harbors tumor-suppressive properties by inhibiting the oncogenic roles of PARP1 or CTCF and plays crucial roles in all-trans-retinoic-acid-mediated therapeutic effects on NB. Administration of FOXD3-AS1 construct or siRNAs against PARP1 or CTCF reduces the tumor growth and prolongs the survival of nude mice. These findings suggest that as a risk-associated lncRNA, FOXD3-AS1 inhibits the progression of NB through repressing PARP1-mediated CTCF activation.

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Section: Discussionmentioning

confidence: 60%

Section: Foxd3-as1 Harbors Tumor-suppressive Properties By Repressingmentioning

confidence: 99%

RETRACTED: Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF

Zhao

Huang

et al. 2018

Molecular Therapy

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“…The chromosome architectural proteins CTCF and cohesin are recruited to sites of DNA damage 19 . CTCF occupancy increases both at binding sites flanking γ-H2AX domains 18 and at sites of DNA lesions 17 after DNA damage is induced.…”

Section: Tad Boundary Strength and Ctcf Loops Increase After Exposurementioning

confidence: 99%

“…This suggests that changes in the structure of local genome domains may happen at a broader scale after IR. Additionally, CCCTC-binding factor (CTCF) and cohesin have been shown to be early responders to DNA damage induced by IR 17,18,19,20 . These proteins have also been recently demonstrated to play significant roles in chromosome folding 21,22,23,24 , contributing to the formation of topologically associating domains (TADs).…”

mentioning

confidence: 99%

Radiation-Induced DNA Damage and Repair Effects on 3D Genome Organization

Sanders

Freeman

et al. 2019

Preprint

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The three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. Fibroblasts, lymphoblasts, and ATM-deficient fibroblasts were irradiated with 5 Gy X-rays and Hi-C was performed after 30 minutes, 24 hours, or 5 days after irradiation. 3D genome changes after irradiation were cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repairproficient cell types exhibited an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation was not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.2 Translocations, deletions, and other genomic aberrations that may follow DNA damage can lead to cancer by directly mutating genes or altering their regulation 7, 8 . Recently, it has become clear that the disruption of 3D genome domains can also be oncogenic 9 . Does the process of DNA repair protect the 3D folding of the genome as well as the linear DNA sequence? Certain cell types are considered to be more radiosensitive than others, but little is known about what contributes to their radiosensitivity. The possibility remains that cell type specific chromosome positioning, along with initial epigenetic chromatin and folding states can influence which translocations occur and how well DNA is able to repair after exposure to IR, helping to explain why certain cell types are more sensitive to radiation 8, 10, 11. Previous studies suggest that DNA repair efficiency may differ for heterochromatin and euchromatin 12,13 . Heterochromatic regions may be more mobile and move to DNA repair sites, where they decondense 14,15 . Condensation or decondensation of specific chromatin regions may not be determined by their preexisting histone modifications 14 , suggesting that other factors may contribute to changes in 3D genome structure after DNA damage. One previous study demonstrated spatial clustering of DSBs in active genes by inducing specific breaks and measuring their interactions with Capture Hi-C 16 . This suggests that changes in the structure of local genome domains may happen at a broader scale after IR. Additionally, CCCTC-binding factor (CTCF) and cohesin have been shown to be early responders to DNA damage induced by IR 17,18,19,20 . These proteins have also been recently demonstrated to play significant roles in chromosome folding 21,22,23,24 , contributing to the formation of topologically associating domains (TADs). These genomic domains intera...

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“…For example, the insulator and transcription factor functions of CTCF have been found to be regulated by PARylation [20,21]. The effect of CTCF PARylation is important in DNA damage response [22]. A number of studies reported direct interaction between CTCF and poly(ADP-ribose) polymerase 1 (PARP1), as well as their co-localization in chromatin [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells

Pavlaki

Chernukhin

Kita

et al. 2017

Preprint

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CTCF is an evolutionary conserved and ubiquitously expressed architectural protein, which regulates a plethora of cellular functions using different molecular mechanisms. The main form of CTCF with an apparent molecular mass of 130 kDa (CTCF130) has been extensively studied, however the properties of CTCF180, highly modified by poly(ADP-ribosyl)ation (PARylation) are not well understood. In this study we performed ChIP-seq and RNA-seq analyses in breast cells 226LDM, proliferating (with CTCF130 as the most abundant CTCF form) and arrested in the cell cycle (with only CTCF180). A dramatic reorganization of CTCF binding was observed during this transition, whereby CTCF was evacuated from many sites ("lost" group), although some sites retained modified CTCF ("common") and others acquired CTCF180 ("gained"). The classic CTCF binding motifs were identified for the former two groups, whereas the latter had no CTCF binding motif. Changes in CTCF occupancies in lost/common (but not gained) sites were associated with increased chromatin densities and altered expression from the neighboring genes. We propose a model integrating CTCF130/180 transition with CTCF-DNA binding and gene expression patterns, and functional outcomes. This study issues an important cautionary note concerning design and interpretation of any experiments using cells and tissues where CTCF180 may be present.

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CTCF participates in DNA damage response via poly(ADP-ribosyl)ation

Cited by 27 publications

References 40 publications

RETRACTED: Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF

RETRACTED: Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF

Radiation-Induced DNA Damage and Repair Effects on 3D Genome Organization

Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells

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