DNA Methylation as an Epigenetic Memory Keeper during Skin Development and Regeneration

2018 ◽  
pp. 57-73
Author(s):  
Ya-Chen Liang ◽  
Randall Widelitz ◽  
Cheng-Ming Chuong
Keyword(s):  
Dna Methylation ◽  
Epigenetic Memory ◽  
Skin Development

scholarly journals Epigenetic dynamics of centromeres and neocentromeres in Cryptococcus deuterogattii

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009743
Author(s):  
Klaas Schotanus ◽  
Vikas Yadav ◽  
Joseph Heitman
Keyword(s):  
Dna Methylation ◽  
Transposable Element ◽  
Fungal Pathogen ◽  
Fusion Partner ◽  
Epigenetic Memory ◽  
Chromosome Fusion ◽  
Human Fungal Pathogen ◽  
Chromosome Fusions ◽  
The Impact ◽  
Active Centromere

Deletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres do not and instead span actively expressed genes. To explore the epigenetic organization of neocentromeres, we analyzed the distribution of the heterochromatic histone modification H3K9me2, 5mC DNA methylation and the euchromatin mark H3K4me2. Native centromeres are enriched for both H3K9me2 and 5mC DNA methylation marks and are devoid of H3K4me2, while neocentromeres do not exhibit any of these features. Neocentromeres in cen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is inactivated and the native centromere of the chromosome fusion partner remains as the sole, active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted the re-activation of the inactive neocentromere. Our results show that the inactive neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To study the impact of transcription on centromere stability, the actively expressed URA5 gene was introduced into the CENP-A bound regions of a native centromere. The introduction of the URA5 gene led to a loss of CENP-A from the native centromere, and a neocentromere formed adjacent to the native centromere location. Remarkably, the inactive, native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. A cumulative analysis of multiple CENP-A distribution profiles revealed centromere drift in C. deuterogattii, a previously unreported phenomenon in fungi. The CENP-A-binding shifted within the ORF-free regions and showed a possible association with a truncated transposable element. Taken together, our findings reveal that neocentromeres in C. deuterogattii are highly unstable and are not marked with an epigenetic memory, distinguishing them from native centromeres.

Epigenetic memory marks determine epiallele stability at loci targeted by de novo DNA methylation

Nature Plants ◽  
2020 ◽  
Vol 6 (6) ◽  
pp. 661-674 ◽  
Author(s):  
Jingwen Li ◽  
Dong-Lei Yang ◽  
Huan Huang ◽  
Guiping Zhang ◽  
Li He ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Epigenetic Memory

scholarly journals Epigenetic Memory of Early-Life Parental Perturbation: Dopamine Decrease and DNA Methylation Changes in Offspring

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Laura Bordoni ◽  
Cinzia Nasuti ◽  
Antonio Di Stefano ◽  
Lisa Marinelli ◽  
Rosita Gabbianelli
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Global Dna Methylation ◽  
Dopamine Level ◽  
Postnatal Exposure ◽  
Epigenetic Memory ◽  
Adult Age ◽  
Dopaminergic Neurodegeneration ◽  
Parental Exposure ◽  
Early Life Exposure

Early-life exposure (from postnatal day 6 to postnatal day 21) to permethrin has been associated with long-term development of dopaminergic neurodegeneration in rats. Here, we first investigated if the dopamine decrease observed following early postnatal exposure to permethrin, an oxidative stressor, can impair the dopamine level in the brain of their untreated offspring. Secondly, we evaluated whether this adverse event affects the epigenome of both directly exposed rats (F0) and their untreated offspring (F1). The results show that early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age. Furthermore, parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated (72.72% and 47.35%, respectively). About 2/3 of pups from exposed mothers showed a significant reduction in dopamine level compared to controls. Global DNA methylation and hydroxymethylation impairment was associated with the F1 pups that showed reduced dopamine. This study provides pivotal evidences on intergenerational effects of postnatal exposure to permethrin emphasizing that this xenobiotic can influence the epigenetic memory of early-life parental perturbations disturbing offspring health.

scholarly journals Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues

2013 ◽  
Vol 45 (10) ◽  
pp. 1198-1206 ◽  
Author(s):  
Gary C Hon ◽  
Nisha Rajagopal ◽  
Yin Shen ◽  
David F McCleary ◽  
Feng Yue ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adult Mouse ◽  
Epigenetic Memory ◽  
Mouse Tissues

DNA methylation and transgenerational epigenetic memory in plants

2009 ◽  
Vol 2009 (Spring) ◽  
Author(s):  
Jerzy Paszkowski ◽  
Olivier Mathieu ◽  
Jon Reinders ◽  
Marie Miruse ◽  
Etienne Bucher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Memory

scholarly journals Neocentromeres lack epigenetic memory and hallmarks of native centromeres in Cryptococcus deuterogattii

2020 ◽  
Author(s):  
Klaas Schotanus ◽  
Vikas Yadav ◽  
Joseph Heitman
Keyword(s):  
Dna Methylation ◽  
Transposable Element ◽  
Fungal Pathogen ◽  
Fusion Partner ◽  
Epigenetic Memory ◽  
Chromosome Fusion ◽  
Human Fungal Pathogen ◽  
Dna Modifications ◽  
Chromosome Fusions ◽  
Active Centromere

AbstractDeletion of native centromeres in the human fungal pathogen Cryptococcus deuterogattii leads to neocentromere formation. Native centromeres span truncated transposable elements, while neocentromeres span actively expressed genes. Neocentromeres in cen10Δ mutants are unstable and chromosome-chromosome fusions occur. After chromosome fusion, the neocentromere is silenced and the native centromere of the chromosome fusion partner remains as the sole active centromere. In the present study, the active centromere of a fused chromosome was deleted to investigate if epigenetic memory promoted re-activation of a silenced neocentromere. Our results show that the silenced neocentromere is not re-activated and instead a novel neocentromere forms directly adjacent to the deleted centromere of the fused chromosome. To explore the epigenetic organization of neocentromeres, we characterized the distribution of the heterochromatic histone modification H3K9me2 and 5mC DNA methylation. Native centromeres were enriched for both H3K9me2 and 5mC DNA methylation marks, while neocentromeres lacked these specific histone and DNA modifications. To study centromere dynamics, the actively expressed URA5 gene was introduced into a native centromere. Introduction of the URA5 gene led to loss of CENP-A from the native centromere, and a neocentromere formed directly adjacent to the native centromere location. Remarkably, the silenced native centromere remained enriched for heterochromatin, yet the integrated gene was expressed and devoid of H3K9me2. Analysis of multiple CENP-A distribution profiles revealed centromere drift in C. deuterogattii, a previously unknown phenomenon in fungi. The CENP-A-enriched region shifted within the pericentric regions, and a truncated transposable element in centromere 5 acted as a barrier between the CENP-A-associated regions of chromatin. Interestingly, this truncated transposable element was devoid of CENP-A binding or H3K9me2 modification and was instead marked by 5mC DNA methylation. Taken together, our findings reveal novel aspects about the epigenetic mechanisms that distinguish native centromeres and neocentromeres.

scholarly journals Dppa2/4 Counteract De Novo Methylation to Establish a Permissive Epigenome for Development

2020 ◽  
Author(s):  
Kristjan H. Gretarsson ◽  
Jamie A. Hackett
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Developmental Competence ◽  
Epigenetic Memory ◽  
Mammalian Development ◽  
Dna Hypomethylation ◽  
Lineage Specification ◽  
Regulatory Pathways ◽  
Genome Wide ◽  
Early Mammalian Development

ABSTRACTEarly mammalian development entails genome-wide epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening in ESC. We identify key genes and regulatory pathways that drive global DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states. In their absence, developmental genes and evolutionary-young LINE1 elements, which DPPA2 specifically binds, lose H3K4me3 and gain ectopic de novo DNA methylation in pluripotent cells. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt the pluripotent epigenome by facilitating H3K4me3 and bivalency to counteract de novo methylation; a function co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.

scholarly journals Integrative Omics analyses reveal epigenetic memory in diabetic renal cells regulating genes associated with kidney dysfunction.

2020 ◽  
Author(s):  
Ada Admin ◽  
Anita Bansal ◽  
Sreeram Balasubramanian ◽  
Sangeeta Dhawan ◽  
Amy Leung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Target Genes ◽  
Major Complication ◽  
Promoter Hypermethylation ◽  
Chromatin Accessibility ◽  
Metabolic Memory ◽  
Epigenetic Memory ◽  
Motif Analysis

Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal failure. Epigenetics has been associated with metabolic memory, in which prior periods of hyperglycemia enhance the future risk of developing DKD despite subsequent glycemic control. To understand the mechanistic role of such epigenetic memory in human DKD and identify new therapeutic targets, we profiled gene expression, DNA methylation, and chromatin accessibility in kidney proximal tubule epithelial cells (PTECs) derived from non-diabetic and Type-2 diabetic (T2D) subjects. T2D-PTECs displayed persistent gene expression and epigenetic changes with and without TGFβ1 treatment, even after culturing <i>in vitro</i> under similar conditions as non-diabetic PTECs, signified by deregulation of fibrotic and transport associated genes (TAGs). Motif-analysis of differential DNA methylation and chromatin accessibility regions associated with genes differentially regulated in T2D revealed enrichment for SMAD3, HNF4A, and CTCF transcription factor binding sites. Furthermore, the downregulation of several TAGs in T2D (including <i>CLDN10</i>, <i>CLDN14</i>, <i>CLDN16</i>, <i>SLC16A2</i>, <i>SLC16A5</i>) was associated with promoter hypermethylation, decreased chromatin accessibility and reduced enrichment of HNF4A, histone H3-lysine-27-acetylation, and CTCF. Together, these integrative analyses reveal epigenetic memory underlying the deregulation of key target genes in T2D-PTECs that may contribute to sustained renal dysfunction in DKD.

scholarly journals Integrative Analysis of Methylome and Transcriptome Reveals the Regulatory Mechanisms of Hair Follicle Morphogenesis in Cashmere Goat

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 969 ◽  
Author(s):  
Shanhe Wang ◽  
Fang Li ◽  
Jinwang Liu ◽  
Yuelang Zhang ◽  
Yujie Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Hair Follicle ◽  
Cashmere Goat ◽  
Rna Seq ◽  
Skin Development ◽  
Follicle Differentiation ◽  
Differentiation Stage ◽  
Hair Morphogenesis ◽  
Induction Stage

Studies in humans and mice have revealed that hair follicle morphogenesis relies on tightly coordinated ectodermal–mesodermal interactions, involving multiple signals and regulatory factors. DNA methylation and long non-coding RNA (lncRNA) play a critical role in early embryonic skin development by controlling gene expression. Acting as an indirect regulator, lncRNA could recruit DNA methyltransferases to specific genomic sites to methylate DNA. However, the molecular regulation mechanisms underlying hair follicle morphogenesis is unclear in cashmere goat. In this study, RNA-seq and whole-genome bisulfite sequencing (WGBS) in embryonic day 65 (E 65) and E 120 skin tissues of cashmere goat were used to reveal this complex regulatory process. The RNA-seq, qRT-PCR, and immunohistochemistry results showed that Wnt signaling played an important role in both hair follicle induction and differentiation stage; transcriptional factors (TFs), including HOXC13, SOX9, SOX21, JUNB, LHX2, VDR, and GATA3, participated in hair follicle differentiation via specific expression at E 120. Subsequently, the combination of WGBS and RNA-seq analysis showed that the expression of some hair follicle differentiation genes and TF genes were negatively correlated with the DNA methylation level generally. A portion of hair follicle differentiation genes were methylated and repressed in the hair follicle induction stage but were subsequently demethylated and expressed during the hair follicle differentiation stage, suggesting that DNA methylation plays an important role in hair morphogenesis by regulating associated gene expression. Furthermore, 45 upregulated and 147 downregulated lncRNAs in E 120 compared with E 65 were identified by lncRNA mapping, and then the potential differentially expressed lncRNAs associated with DNA methylation on the target gene were revealed. In conclusion, critical signals and genes were revealed during hair follicle morphogenesis in the cashmere goat. In this process, DNA methylation was lower in the hair follicle differentiation compared with the hair follicle induction stage and may play an important role in hair morphogenesis by regulating associated gene expression. Furthermore, potential lncRNAs associated with DNA methylation on target genes were delineated. This study enriches the regulatory network and molecular mechanisms on hair morphogenesis.

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