亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Unraveling the Epigenetic Basis of Liver Development, Regeneration and Disease

生物 表观遗传学 再生(生物学) 染色质 细胞生物学 神经发生的表观遗传调控 肝再生 细胞分化 遗传学 染色质重塑 基因
作者
Filippo Macchi,Kirsten C. Sadler
出处
期刊:Trends in Genetics [Elsevier]
卷期号:36 (8): 587-597 被引量:21
标识
DOI:10.1016/j.tig.2020.05.002
摘要

An epigenetic prepattern governs fate decisions and differentiation potential during liver development. Liver regeneration is accompanied by a coordinated set of gene expression changes, which could be regulated by an epigenetic pattern in quiescent hepatocytes, thereby governing regenerative potential. Recent studies suggest that broad changes to the epigenetic landscape during liver regeneration control the expression of genes driving regeneration and the ones dictating hepatic fate. A wealth of studies over several decades has revealed an epigenetic prepattern that determines the competence of cellular differentiation in the developing liver. More recently, studies focused on the impact of epigenetic factors during liver regeneration suggest that an epigenetic code in the quiescent liver may establish its regenerative potential. We review work on the pioneer factors and other chromatin remodelers that impact the gene expression patterns instructing hepatocyte and biliary cell specification and differentiation, along with the requirement of epigenetic regulatory factors for hepatic outgrowth. We then explore recent studies involving the role of epigenetic regulators, Arid1a and Uhrf1, in efficient activation of proregenerative genes during liver regeneration, thus highlighting the epigenetic mechanisms of liver disease and tumor development. A wealth of studies over several decades has revealed an epigenetic prepattern that determines the competence of cellular differentiation in the developing liver. More recently, studies focused on the impact of epigenetic factors during liver regeneration suggest that an epigenetic code in the quiescent liver may establish its regenerative potential. We review work on the pioneer factors and other chromatin remodelers that impact the gene expression patterns instructing hepatocyte and biliary cell specification and differentiation, along with the requirement of epigenetic regulatory factors for hepatic outgrowth. We then explore recent studies involving the role of epigenetic regulators, Arid1a and Uhrf1, in efficient activation of proregenerative genes during liver regeneration, thus highlighting the epigenetic mechanisms of liver disease and tumor development. a technique to determine the chromatin accessibility across the whole genome. contain a structural motif (the bromodomain) that recognizes acetylated lysine residues on histones. BET inhibitors block interaction between BET proteins and are used as cancer therapy due to the frequent deregulation of BETs in cancer. chromatin immunoprecipitation is a technique to determine DNA–protein interaction. It can be performed to detect the binding sites of transcription/repressive factors or to determine the pattern of hPTMs and histone variants. these are protein complexes that use ATP to restructure nucleosome position. These include the SWI/SNF complex, which contains Arid1a and the BETs. DNA methylation is the most studied DNA modification, and it occurs at the 5-methylcitosine in the CG dinucleotide (CpG). DNA methylation causes a condensation of the DNA fibers; thus, it is involved in imprinting and repression of repetitive elements, such as retrotransposons. Even if numerous studies show a correlation between hypermethylation of gene promoters and gene silencing, there is no evidence that DNA methylation controls gene expression in terminal differentiated tissues. In fact, most gene promoters are devoid of DNA methylation. During the cell cycle, DNA methylation is maintained by DNA methyltransferase 1 (Dnmt1) that is recruited by ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) on the hemimethylated site at the replication forks. De novo DNA methylation is carried out by DNMT3A and DNMT3B in mammals. the modifications that control genome regulation and accessibility without affecting its sequence. The epigenome is central to regulating gene transcription, TE suppression, cell fate, and differentiation. acetylation of histone tails by histone acetyltransferases (HATs, such as p300) in H3K27ac, H3K9ac, or H3K14ac open the chromatin. Histone deacetylases (HDACs) reverse this and lead to closed chromatin. HDAC inhibitors are used to keep the chromatin open but these also target many other acetyltransferases. histone tails can undergo more than 60 different PTMs, such as methylation, acetylation, ubiquitylation, sumoylation, phosphorylation, ADP ribosylation, and proline isomerization. This combination is referred to as the ‘histone code.’ Each of these modifications regulate the accessibility of the chromatin by compacting or dispersing the nucleosomes. Although, typically, histone methylations condense the nucleosomes (i.e., methylation of lysine 9 of histone 3 -H3K9me1me2me3- or trimethylation of lysine 27 of histone 3 -H3K27me3-). Exceptions include: H3K4me3, associated to active promoter region of transcribed genes, and H3K4me1, localized to active enhancers. histone variants are noncanonical variants of histones, containing one or a few different amino acids that are usually expressed at low levels compared to the canonical version. They have specific expression patterns in different tissues and time of development, and they specifically localize in distinct regions of the genome, affecting hPTMs and chromatin regulation. the fundamental structural unit of the chromatin. Each nucleosome is composed of 146 bp of DNA wrapped around eight core proteins called histones. Each octamer is composed of two copies of H2A, H2B, H3, and H4. The nucleosomes are connected by linker DNA and one linker histone, H1 or H5. a class of TFs that possess the unique ability to initiate chromatin opening by engaging their target sites with displacement of the linker histones. They also recruit chromatin remodeling complexes and tissue-specific regulatory TFs and are important for several developmental processes. these ‘jumping genes’, also called transposons, discovered by McClintock, are remnants of ancient viruses that have become incorporated into the genomes of most organisms. TEs are repetitive sequences found in multiple copies due to their mobility. While most TEs have degenerated during evolution so they no longer pose a threat, the potential damage that mobile DNA can have on genome structure has resulted in the evolution mechanisms of suppressing TE activation. In vertebrates, most TEs are suppressed by DNA methylation as well as other repressive epigenetic marks.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
3秒前
immm发布了新的文献求助10
10秒前
10秒前
HeHe发布了新的文献求助10
13秒前
livialiu发布了新的文献求助10
16秒前
19秒前
李健应助酷酷豌豆射手采纳,获得10
29秒前
葛觅荷发布了新的文献求助10
32秒前
葛觅荷完成签到,获得积分10
39秒前
suity完成签到,获得积分10
41秒前
酷酷豌豆射手完成签到,获得积分10
45秒前
45秒前
SciGPT应助王十三采纳,获得10
49秒前
1分钟前
you发布了新的文献求助10
1分钟前
香妃发布了新的文献求助10
1分钟前
you完成签到,获得积分10
1分钟前
1分钟前
丘比特应助you采纳,获得10
1分钟前
1分钟前
JamesPei应助科研通管家采纳,获得10
1分钟前
1分钟前
1分钟前
王十三发布了新的文献求助10
1分钟前
1分钟前
科研人完成签到 ,获得积分10
1分钟前
1分钟前
2分钟前
2分钟前
花半里里发布了新的文献求助10
2分钟前
wanci应助花半里里采纳,获得10
2分钟前
小不点、大迷糊完成签到,获得积分10
2分钟前
ZhangDaying完成签到 ,获得积分10
2分钟前
2分钟前
小北发布了新的文献求助10
2分钟前
Akim应助开心小阮采纳,获得10
2分钟前
快哒哒哒完成签到,获得积分10
2分钟前
struggling2026完成签到 ,获得积分10
2分钟前
吕懿发布了新的文献求助10
2分钟前
yaoyaoyao完成签到 ,获得积分10
3分钟前
高分求助中
Un calendrier babylonien des travaux, des signes et des mois: Séries iqqur îpuš 1036
Sustainable Land Management: Strategies to Cope with the Marginalisation of Agriculture 1000
Corrosion and Oxygen Control 600
Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity 500
重庆市新能源汽车产业大数据招商指南(两链两图两池两库两平台两清单两报告) 400
Division and square root. Digit-recurrence algorithms and implementations 400
行動データの計算論モデリング 強化学習モデルを例として 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2545351
求助须知:如何正确求助?哪些是违规求助? 2175631
关于积分的说明 5600124
捐赠科研通 1896314
什么是DOI,文献DOI怎么找? 946215
版权声明 565334
科研通“疑难数据库(出版商)”最低求助积分说明 503541