
체중 감량 후에도 지방 조직에는 비만의 흔적이 후성유전학적으로 남아있어 요요 현상을 일으키고 건강 관리를 어렵게 만든다.


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Stable epigenetic changes indicate the existence of an obesogenic memory in mouse adipocytes that primes cells for pathological responses in an obesogenic environment and potentially contributes to the problematic ‘yo-yo’ effect often seen with dieting.

Adipose tissue retains an epigenetic memory of obesity after weight loss - Nature

체중-감량-후에도-지방-조직에-남아있는-비만의-후성유전학적-기억


체중 감량 후에도 지방 조직에 남아있는 비만의 후성유전학적 기억


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Weight loss does not erase the obesogenic memory in adipose tissue; epigenetic changes persist and contribute to accelerated weight regain and metabolic dysfunction.


adipose-tissue-retains-an-epigenetic-memory-of-obesity-even-after-weight-loss-contributing-to-weight-regain


Adipose Tissue Retains an Epigenetic Memory of Obesity Even After Weight Loss, Contributing to Weight Regain



The transcription factor NRL, crucial for rod photoreceptor development, interacts with RNA-binding proteins and R-loops, revealing a complex regulatory network governing gene expression in retinal cells.


RNA-binding proteins (RBPs) perform diverse functions including the regulation of chromatin dynamics and the coupling of transcription with RNA processing. However, our understanding of their actions in mammalian neurons remains limited. Using affinity purification, yeast-two-hybrid and proximity ligation assays, we identified interactions of multiple RBPs with NRL, a Maf-family bZIP transcription factor critical for retinal rod photoreceptor development and function. In addition to splicing, many NRL-interacting RBPs are associated with R-loops, which form during transcription and increase during photoreceptor maturation. Focusing on DHX9 RNA helicase, we demonstrate that its expression is modulated by NRL and that the NRL-DHX9 interaction is positively influenced by R-loops. ssDRIP-Seq analysis reveals both stranded and unstranded R-loops at distinct genomic elements, characterized by active and inactive epigenetic signatures and enriched at neuronal genes. NRL binds to both types of R-loops, suggesting an epigenetically independent function. Our findings suggest additional functions of NRL during transcription and highlight complex interactions among transcription factors, RBPs, and R-loops in regulating photoreceptor gene expression in the mammalian retina.

### Competing Interest Statement

The authors have declared no competing interest.

Maf-family bZIP transcription factor NRL interacts with RNA-binding proteins and R-loops in retinal photoreceptors

nrl-a-maf-family-bzip-transcription-factor-essential-for-retinal-rod-photoreceptor-development-interacts-with-rna-binding-proteins-and-r-loops-to-regulate-gene-expression


NRL, a Maf-family bZIP Transcription Factor Essential for Retinal Rod Photoreceptor Development, Interacts with RNA-Binding Proteins and R-Loops to Regulate Gene Expression



胞嘧啶-5 DNA 甲基化 (5mC) 會增加細胞對氧化損傷的敏感性，這可能是某些物種在進化過程中完全喪失 5mC 的原因。


DNA methylation at the 5 position of cytosine (5mC) is an ancient epigenetic mark in eukaryotes. The levels of total 5mC vary enormously between different species, and the DNA methyltransferases that introduce 5mC have been repeatedly lost in several independent lineages. DNA methyltransferases are a threat to genomic stability due to the increased mutagenicity of 5mC bases and the propensity of DNA methyltransferases themselves to introduce DNA alkylation damage as an off-target effect. However, whether alkylation damage explains why 5mC is frequently lost in evolution is unclear. Here we tested the fitness consequences of DNA methyltransferase-induced alkylation damage by introducing a eukaryotic-like 5mC system into E. coli . We showed that introducing 5mC genome-wide leads to increased sensitivity to alkylating agents, which is strongly enhanced by removal of the 3mC repair enzyme AlkB. Unexpectedly, we discovered that 5mC introduction led to increased sensitivity to oxidative stress. We showed that this is due to increased formation of reactive oxygen in the presence of 5mC. We determined that reactive oxygen species led to non-enzymatic oxidation of 5mC, producing modified cytosines such as 5fC that are recognised as DNA base damage in E. coli . Overall, our work identifies increased sensitivity to oxidative stress, as well as alkylating agents, as a negative consequence of genome-wide 5mC. Oxidative stress is frequently encountered by organisms in their environment, thus offering a plausible reason for total loss of 5mC in some species.

### Competing Interest Statement

The authors have declared no competing interest.

Introduction of cytosine-5 DNA methylation sensitizes cells to oxidative damage

細胞中胞嘧啶-5-dna-甲基化的引入會增加細胞對氧化損傷的敏感性


細胞中胞嘧啶-5 DNA 甲基化的引入會增加細胞對氧化損傷的敏感性



DNA 메틸화는 유전자 발현 조절에 중요한 역할을 하지만, 세포를 산화 스트레스에 취약하게 만들어 DNA 손상을 증가시킬 수 있다.


세포-내-5mc-dna-메틸화-도입은-산화적-손상에-대한-민감성을-증가시킨다


세포 내 5mC DNA 메틸화 도입은 산화적 손상에 대한 민감성을 증가시킨다



While cytosine-5 DNA methylation (5mC) is an ancient epigenetic mark, its presence increases sensitivity to oxidative stress due to the formation of modified cytosines like 5fC, which are recognized as DNA damage, potentially explaining the loss of 5mC in some species.


genome-wide-cytosine-5-dna-methylation-increases-sensitivity-to-oxidative-stress-and-alkylating-agents-in-e-coli


Genome-wide cytosine-5 DNA methylation increases sensitivity to oxidative stress and alkylating agents in E. coli



本文揭示了細菌嗜熱脂肪芽孢桿菌 (BtFd) 中的 Asp64 質子化狀態作為低電位鐵氧還蛋白 [4Fe-4S] 簇氧化還原穩定性的內在控制因素。


Ferredoxin is a small iron-sulfur protein and acts as an electron carrier. Low-potential ferredoxins harbor [4Fe-4S] cluster(s), which play(s) a crucial role as the redox center. Low-potential ferredoxins are able to cover a wide range of redox potentials (−700 to −200 mV); however, the mechanisms underlying the factors which control the redox potential are still enigmatic. Here, we determined the neutron structure of ferredoxin from Bacillus thermoproteolyticus , and experimentally revealed the exact hydrogen-bonding network involving the [4Fe-4S] cluster. The density functional theory calculations based on the hydrogen-bonding network revealed that protonation states of the sidechain of Asp64 close to the [4Fe-4S] cluster critically affected the stability of the reduced state in the cluster. These findings provide the first identification of the intrinsic control factor of redox potential for the [4Fe-4S] cluster in low-potential ferredoxins.

### Competing Interest Statement

The authors have declared no competing interest.

Protonation/deprotonation-driven switch for the redox stability of low-potential [4Fe-4S] ferredoxin

低電位鐵氧還蛋白氧化還原穩定性的質子化-去質子化驅動開關


低電位鐵氧還蛋白氧化還原穩定性的質子化/去質子化驅動開關



저전위 페레독신에서 [4Fe-4S] 클러스터 근처 Asp64 잔기의 양성자화 상태가 전자 전달 과정에서 환원 상태의 안정성을 제어하는 스위치 역할을 한다.


저전위-페레독신의-산화환원-안정성을-제어하는-양성자화-탈양성자화-스위치-메커니즘-규명


저전위 페레독신의 산화환원 안정성을 제어하는 양성자화/탈양성자화 스위치 메커니즘 규명



低電位フェレドキシンにおいて、[4Fe-4S]クラスター近傍のアスパラギン酸残基の側鎖のプロトン化状態が、還元状態の安定性に影響を与え、酸化還元電位を制御する重要な役割を果たしている。


低電位フェレドキシンにおける酸化還元安定性のプロトン化-脱プロトン化駆動スイッチ


低電位フェレドキシンにおける酸化還元安定性のプロトン化/脱プロトン化駆動スイッチ



The protonation state of a conserved aspartate residue (Asp64 in Bacillus thermoproteolyticus ferredoxin) acts as a switch, controlling the redox potential and electron transfer in low-potential [4Fe-4S] and [3Fe-4S] ferredoxins.


protonation-deprotonation-of-a-conserved-aspartate-residue-determines-the-redox-potential-of-low-potential-ferredoxin


Protonation/Deprotonation of a Conserved Aspartate Residue Determines the Redox Potential of Low-Potential Ferredoxin
