SMARCAL1 Negatively Regulates C-Myc Transcription By Altering The Conformation Of The Promoter Region

Sharma, Tapan; Bansal, Ritu; Haokip, Dominic Thangminlen; Goel, Isha; Muthuswami, Rohini

doi:10.1038/srep17910

Cited by 22 publications

(31 citation statements)

References 47 publications

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“…Consistent with this, we previously observed that SMARCAL1 homologues bind transcriptionally active chromatin and modulate gene expression [13]. Sharma et al (2015) recently showed that the bovine orthologue of SMARCAL1 negatively and directly regulates the transcription of MYC by altering the conformation of its promoter [34]. Alternatively, because stalled replication forks induce epigenetic changes that alter gene expression [35, 36], impedance of DNA replication fork restart by SMARCAL1 deficiency might contribute to the changes in gene expression.…”

Section: Discussionsupporting

confidence: 65%

Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?

Morimoto

Myung

Beirnes

et al. 2016

Orphanet J Rare Dis

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BackgroundSchimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily A-like 1 (SMARCAL1) gene. Changes in gene expression underlie the arteriosclerosis and T-cell immunodeficiency of SIOD; therefore, we hypothesized that SMARCAL1 deficiency causes the focal segmental glomerulosclerosis (FSGS) of SIOD by altering renal gene expression. We tested this hypothesis by gene expression analysis of an SIOD patient kidney and verified these findings through immunofluorescent analysis in additional SIOD patients and a genetic interaction analysis in Drosophila.ResultsWe found increased expression of components and targets of the Wnt and Notch signaling pathways in the SIOD patient kidney, increased levels of unphosphorylated β-catenin and Notch1 intracellular domain in the glomeruli of most SIOD patient kidneys, and genetic interaction between the Drosophila SMARCAL1 homologue Marcal1 and genes of the Wnt and Notch signaling pathways.ConclusionsWe conclude that increased Wnt and Notch activity result from SMARCAL1 deficiency and, as established causes of FSGS, contribute to the renal disease of most SIOD patients. This further clarifies the pathogenesis of SIOD and will hopefully direct potential therapeutic approaches for SIOD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0519-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 65%

Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?

Morimoto

Myung

Beirnes

et al. 2016

Orphanet J Rare Dis

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“…SMARCAL1 also has been reported to have a regulatory role in the transcription of a subset of genes (Baradaran-Heravi et al , 2012b, Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017). Specifically, SMARCAL1 was reported to directly modify the chromatin near promoter sequences to regulate gene expression especially in cells experiencing replication stress (Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017).…”

Section: Smarcal1mentioning

confidence: 99%

“…Specifically, SMARCAL1 was reported to directly modify the chromatin near promoter sequences to regulate gene expression especially in cells experiencing replication stress (Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017). However, SMARCAL1 binds DNA in a sequence independent manner and has not been found in complexes with any transcription factors or components of ATP-dependent chromatin remodeling complexes (Betous et al , 2012).…”

Section: Smarcal1mentioning

confidence: 99%

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Poole

Chen

2017

Critical Reviews in Biochemistry and Molecular Biology

115

105

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A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. These proteins are recruited to replication forks through protein-protein interactions and bind DNA using both their motor and substrate recognition domains (SRD). The SRD provides specificity to DNA structures like forks and junctions and confer DNA remodeling activity to the motor domains. Remodeling reactions include fork reversal and branch migration to promote fork stabilization, template switching, and repair. Regulation ensures these powerful activities remain controlled and restricted to damaged replication forks. Inherited mutations in SMARCAL1 cause a severe developmental disorder and mutations in ZRANB3 and HLTF are linked to cancer illustrating the importance of these enzymes in ensuring complete and accurate DNA replication. In this review, we examine how these proteins function, concentrating on their common and unique attributes and regulatory mechanisms.

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“…All cell lines were purchased from National Centre for Cell Science, Pune, India, and cultured as detailed previously [36,38]. Transfections were done RNA isolation, cDNA preparation and qPCR: Total RNA was extracted and cDNA was prepared using the established protocol [36].…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Regulation of ATM and ATR by Smarcal1 and BRG1

Sethy

Radhakrishnan

Patne

et al. 2018

Preprint

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The G2/M checkpoint is activated on DNA damage by the ATM and ATR kinases that are regulated by post-translational modifications. In this paper, the transcriptional coregulation of ATM and ATR by SMARCAL1 and BRG1, both members of the ATPdependent chromatin remodeling protein family, is described. SMARCAL1 and BRG1 colocalize on the promoters of ATM and ATR; downregulation of SMARCAL1/BRG1 results in transcriptional repression of ATM/ATR and therefore, overriding of the G2/M checkpoint leading to mitotic abnormalities. On doxorubicin-induced DNA damage, SMARCAL1 and BRG1 are upregulated and in turn, upregulate the expression of ATM/ATR. Phosphorylation of ATM/ATR is needed for the transcriptional upregulation of SMARCAL1 and BRG1, and therefore, of ATM and ATR on DNA damage. The regulation of ATM/ATR is rendered non-functional if SMARCAL1 and/or BRG1 are absent or if the two proteins are mutated such that they are unable to hydrolyze ATP, as in for example in Schimke Immuno-Osseous Dysplasia and Coffin-Siris Syndrome. Thus, an intricate transcriptional regulation of DNA damage response genes mediated by SMARCAL1 and BRG1 is present in mammalian cells.

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SMARCAL1 Negatively Regulates C-Myc Transcription By Altering The Conformation Of The Promoter Region

Cited by 22 publications

References 47 publications

Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?

Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Regulation of ATM and ATR by Smarcal1 and BRG1

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