Abstract:
:Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has long been known as a master transcriptional repressor of autophagy. Here, we identify a novel role for ZKSCAN3 in alleviating senescence that is independent of its autophagy-related activity. Downregulation of ZKSCAN3 is observed in aged human mesenchymal stem cells (hMSCs) and depletion of ZKSCAN3 accelerates senescence of these cells. Mechanistically, ZKSCAN3 maintains heterochromatin stability via interaction with heterochromatin-associated proteins and nuclear lamina proteins. Further study shows that ZKSCAN3 deficiency results in the detachment of genomic lamina-associated domains (LADs) from the nuclear lamina, loss of heterochromatin, a more accessible chromatin status and consequently, aberrant transcription of repetitive sequences. Overexpression of ZKSCAN3 not only rescues premature senescence phenotypes in ZKSCAN3-deficient hMSCs but also rejuvenates physiologically and pathologically senescent hMSCs. Together, these data reveal for the first time that ZKSCAN3 functions as an epigenetic modulator to maintain heterochromatin organization and thereby attenuate cellular senescence. Our findings establish a new functional link among ZKSCAN3, epigenetic regulation, and stem cell aging.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Hu H,Ji Q,Song M,Ren J,Liu Z,Wang Z,Liu X,Yan K,Hu J,Jing Y,Wang S,Zhang W,Liu GH,Qu Jdoi
10.1093/nar/gkaa425subject
Has Abstractpub_date
2020-06-19 00:00:00pages
6001-6018issue
11eissn
0305-1048issn
1362-4962pii
5840577journal_volume
48pub_type
杂志文章abstract::The Nucleolar Proteome Database (NOPdb) archives data on >700 proteins that were identified by multiple mass spectrometry (MS) analyses from highly purified preparations of human nucleoli, the most prominent nuclear organelle. Each protein entry is annotated with information about its corresponding gene, its domain st...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj004
更新日期:2006-01-01 00:00:00
abstract::The direction of replication of DNA within replicons of Physarum polycephalum was studied by pulse-labelling with 5-bromouracil-deoxyriboside (BrdUrd) and 3H-adenosine deoxyriboside (dAdo), followed by ultraviolet- (UV) -photolysis and analysis of molecular weights of single strand DNA fragments on alkaline sucrose gr...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:1988-09-12 00:00:00
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journal_title:Nucleic acids research
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更新日期:2018-02-28 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg403
更新日期:2003-06-15 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2010-06-01 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2012-12-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1992-12-25 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::MicroRNAs (miRNAs) are small RNAs ∼22 nt in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next-generation sequencing applications, have reshaped the miRNA research landscape. In this study, w...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2013-01-01 00:00:00