scholarly journals TET2-interacting long noncoding RNA promotes active DNA demethylation of the MMP-9 promoter in diabetic wound healing

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Liyan Zhou ◽  
Meng Ren ◽  
Tingting Zeng ◽  
Wei Wang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Excision Repair ◽  
Skin Wound ◽  
Dna Demethylation ◽  
Skin Wound Healing ◽  
Active Dna Demethylation ◽  
Diabetic Wound Healing ◽  
Base Excision

Abstract Wound healing in diabetic skin is impaired by excessive activation of matrix metalloproteinase-9 (MMP-9). MMP-9 transcription is activated by Ten-eleven translocation 2 (TET2), a well-known DNA demethylation protein that induces MMP-9 promoter demethylation in diabetic skin tissues. However, how TET2 is targeted to specific loci in the MMP-9 promoter is unknown. Here, we identified a TET2-interacting long noncoding RNA (TETILA) that is upregulated in human diabetic skin tissues. TETILA regulates TET2 subcellular localization and enzymatic activity, indirectly activating MMP-9 promoter demethylation. TETILA also recruits thymine-DNA glycosylase (TDG), which simultaneously interacts with TET2, for base excision repair-mediated MMP-9 promoter demethylation. Together, our results suggest that the TETILA serves as a genomic homing signal for TET2-mediated demethylation specific loci in MMP-9 promoter, thereby disrupting the process of diabetic skin wound healing.

scholarly journals Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine

2011 ◽  
Vol 286 (41) ◽  
pp. 35334-35338 ◽  
Author(s):  
Atanu Maiti ◽  
Alexander C. Drohat
Keyword(s):  
Embryonic Development ◽  
Catalytic Mechanism ◽  
Excision Repair ◽  
Dna Demethylation ◽  
Oxidation Products ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase ◽  
Active Demethylation ◽  
Active Dna Demethylation ◽  
Base Excision

Thymine DNA glycosylase (TDG) excises T from G·T mispairs and is thought to initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent studies show that TDG, including its glycosylase activity, is essential for active DNA demethylation and embryonic development. These and other findings suggest that active demethylation could involve mC deamination by a deaminase, giving a G·T mispair followed by TDG-initiated BER. An alternative proposal is that demethylation could involve iterative oxidation of mC to 5-hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5-carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with conversion of caC to C by a putative decarboxylase. Our previous studies suggest that TDG could excise fC and caC from DNA, which could provide another potential demethylation mechanism. We show here that TDG rapidly removes fC, with higher activity than for G·T mispairs, and has substantial caC excision activity, yet it cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is consistent with its strong specificity for excising bases from a CpG context. Our findings reveal a remarkable new aspect of specificity for TDG, inform its catalytic mechanism, and suggest that TDG could protect against fC-induced mutagenesis. The results also suggest a new potential mechanism for active DNA demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent BER. Such a mechanism obviates the need for a decarboxylase and is consistent with findings that TDG glycosylase activity is essential for active demethylation and embryonic development, as are mechanisms involving TDG excision of deaminated mC or hmC.

Long Noncoding RNA LINC01435 Impedes Diabetic Wound Healing by Facilitating YY1-Mediated HDAC8 Expression

2021 ◽  
Author(s):  
Wan Fu ◽  
Diefei Liang ◽  
Xiaoying Wu ◽  
Hongxing Chen ◽  
Xiaosi Hong ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Diabetic Wound ◽  
Diabetic Wound Healing

scholarly journals Novel Long Noncoding RNA lnc-URIDS Delays Diabetic Wound Healing by Targeting Plod1

Diabetes ◽  
2020 ◽  
Vol 69 (10) ◽  
pp. 2144-2156
Author(s):  
Mengdie Hu ◽  
Yuxi Wu ◽  
Chuan Yang ◽  
Xiaoyi Wang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Diabetic Wound ◽  
Diabetic Wound Healing

scholarly journals Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration

2019 ◽  
Vol 116 (19) ◽  
pp. 9443-9452 ◽  
Author(s):  
Dongqing Li ◽  
Lara Kular ◽  
Manika Vij ◽  
Eva K. Herter ◽  
Xi Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Noncoding Rna ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Dna Methyltransferases ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Protein Coding ◽  
Keratinocyte Migration ◽  
Gene Expression Control

An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-β signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed “wound and keratinocyte migration-associated lncRNA 1” (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.

scholarly journals Long Noncoding RNA GAS5 Regulates Macrophage Polarization and Diabetic Wound Healing

2020 ◽  
Vol 140 (8) ◽  
pp. 1629-1638 ◽  
Author(s):  
Junyi Hu ◽  
Liping Zhang ◽  
Cole Liechty ◽  
Carlos Zgheib ◽  
Maggie M. Hodges ◽  
...  
Keyword(s):  
Wound Healing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Macrophage Polarization ◽  
Diabetic Wound ◽  
Diabetic Wound Healing
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