Epigenetic mechanism of SETDB1 in brain: implications for neuropsychiatric disorders

Zhu, Yueyan; Sun, Daijing; Jakovcevski, Mira; Jiang, Yan

doi:10.1038/s41398-020-0797-7

Cited by 27 publications

(31 citation statements)

References 54 publications

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“…there are several methyltransferases specific for H3K9 trimethylation, including SUV39H1, G9A, GLP, or SETDB1, among others (Zhang et al, 2020). In addition, SETB1 methyltransferase could also trimethylate H3 at lysine 9 (Zhu et al, 2020). On the other hand, histone H1 (Healton et al, 2020) and non-histone proteins, such as HP1 families (Lehnertz et al, 2003), could regulate such modification.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice

et al. 2020

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Post-translational epigenetic modifications take place in mouse neurons of the dentate gyrus (DG) with age. Here, we report that agedependent reduction in H3K9 trimethylation (H3K9me3) is prevented by cyclic induction of the Yamanaka factors used for cell reprogramming. Interestingly, Yamanaka factors elevated the levels of migrating cells containing the neurogenic markers doublecortin and calretinin, and the levels of the NMDA receptor subunit GluN2B. These changes could result in an increase in the survival of newborn DG neurons during their maturation and higher synaptic plasticity in mature neurons. Importantly, these cellular changes were accompanied by an improvement in mouse performance in the object recognition test over long time. We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice

et al. 2020

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“…This is achieved by KRAB–ZFP interacting with SETDB1 in a sequence-specific manner after SETDB1 interaction with KAP1. KAP1 recruits SETDB1, as well as HP1 and the NuRD histone deacetylase complex [ 25 ]. The binding of SETDB1 to H3K9 is achieved via the three Tudor domains, which detect regions of H3 histones containing both K14 acetylation and K9 methylation [ 11 ].…”

Section: Biochemical Features Of Setdb1mentioning

confidence: 99%

Structure, Activity and Function of the SETDB1 Protein Methyltransferase

Markouli

Strepkos

Piperi

2021

Life

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The SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) is a prominent member of the Suppressor of Variegation 3–9 (SUV39)-related protein lysine methyltransferases (PKMTs), comprising three isoforms that differ in length and domain composition. SETDB1 is widely expressed in human tissues, methylating Histone 3 lysine 9 (H3K9) residues, promoting chromatin compaction and exerting negative regulation on gene expression. SETDB1 has a central role in normal physiology and nervous system development, having been implicated in the regulation of cell cycle progression, inactivation of the X chromosome, immune cells function, expression of retroelements and formation of promyelocytic leukemia (PML) nuclear bodies (NB). SETDB1 has been frequently deregulated in carcinogenesis, being implicated in the pathogenesis of gliomas, melanomas, as well as in lung, breast, gastrointestinal and ovarian tumors, where it mainly exerts an oncogenic role. Aberrant activity of SETDB1 has also been implicated in several neuropsychiatric, cardiovascular and gastrointestinal diseases, including schizophrenia, Huntington’s disease, congenital heart defects and inflammatory bowel disease. Herein, we provide an update on the unique structural and biochemical features of SETDB1 that contribute to its regulation, as well as its molecular and cellular impact in normal physiology and disease with potential therapeutic options.

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“…SETDB1 is involved in heterochromatin formation and transcription silencing via histone H3 methyltransferase activity ( Zhu et al, 2020 ). In this study, we found that Setdb1 KD led to the upregulation of Nox4 and E2F1 .…”

Section: Discussionmentioning

confidence: 99%

The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase

Chen

Liu

et al. 2020

Front. Genet.

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SETDB1, a histone H3 lysine 9 (H3K9) methyltransferase, is crucial in meiosis and embryo development. This study aimed to investigate whether SETDB1 was associated with spermatogonial stem cells (SSC) homeostasis. We found that knockdown of Setdb1 impaired cell proliferation, led to an increase in reactive oxygen species (ROS) level through NADPH oxidase, and Setdb1 deficiency activated ROS downstream signaling pathways, including JNK and p38 MAPK, which possibly contributed to SSC apoptosis. Melatonin scavenged ROS and rescued the phenotype of Setdb1 KD. In addition, we demonstrated that SETDB1 regulated NADPH oxidase 4 ( Nox4 ) and E2F1 . Therefore, this study uncovers the new roles of SETDB1 in mediating intracellular ROS homeostasis for the survival of SSC.

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Epigenetic mechanism of SETDB1 in brain: implications for neuropsychiatric disorders

Cited by 27 publications

References 54 publications

In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice

In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice

Structure, Activity and Function of the SETDB1 Protein Methyltransferase

The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase

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