scholarly journals Immunohistochemical Analysis of Histone H3 Modification in Newt Tail Tissue Cells following Amputation

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ji-Wen Wu ◽  
Xu Zhang ◽  
Reiko Sekiya ◽  
Kiyoshi Aoyagi ◽  
Tao-Sheng Li
Keyword(s):  
Stem Cells ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Histone H3 ◽  
Immunohistochemical Analysis ◽  
Regeneration Process ◽  
Proliferating Cells ◽  
Tail Regeneration ◽  
Tissue Cells

Background. Newts have impressive regenerative capabilities, but it remains unclear about the role of epigenetic regulation in regeneration process. We herein investigated histone modifications in newt tail tissue cells following amputation. Methods and Results. Iberian ribbed male newts (6-8 months old) were suffered to about 1.5 cm length of amputation of their tails for initiating regeneration process, and the residual stump of tail tissues was collected for immunohistochemical analysis 3 days later. Compared to the tissue cells of intact tails, c-kit-positive stem cells and PCNA-positive proliferating cells were significantly higher in tails suffered to amputation ( P < 0.001 ). Amputation also significantly induced the acetylation of H3K9, H3K14, and H3K27 in cells of the tails with amputation ( P < 0.001 ), but did not significantly change the methylation of H3K27 ( P = 0.063 ). Conclusion. These results suggest that epigenetic regulation likely involves in newt tail regeneration following amputation.

Epigenetic Regulator Signatures in Regenerative Capacity

2019 ◽  
Vol 14 (7) ◽  
pp. 598-606
Author(s):  
Sarah Albogami
Keyword(s):  
Epigenetic Regulation ◽  
Animal Species ◽  
Current Knowledge ◽  
Regeneration Process ◽  
Body Parts ◽  
Lysine Methylation ◽  
Regenerative Capacity ◽  
Biological Phenomena ◽  
Epigenetic Regulator

Background:: Regeneration is the process by which body parts lost as a result of injury are replaced, as observed in certain animal species. The root of regenerative differences between organisms is still not very well understood; if regeneration merely recycles developmental pathways in the adult form, why can some animals regrow organs whereas others cannot? In the regulation of the regeneration process as well as other biological phenomena, epigenetics plays an essential role. Objective:: This review aims to demonstrate the role of epigenetic regulators in determining regenerative capacity. Results:: In this review, we discuss the basis of regenerative differences between organisms. In addition, we present the current knowledge on the role of epigenetic regulation in regeneration, including DNA methylation, histone modification, lysine methylation, lysine methyltransferases, and the SET1 family. Conclusion:: An improved understanding of the regeneration process and the epigenetic regulation thereof through the study of regeneration in highly regenerative species will help in the field of regenerative medicine in future.

scholarly journals The TAZ2 domain of CBP/p300 directs acetylation towards H3K27 within chromatin

2020 ◽  
Author(s):  
Thomas W. Sheahan ◽  
Viktoria Major ◽  
Kimberly M. Webb ◽  
Elana Bryan ◽  
Philipp Voigt
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Enzymatic Activity ◽  
Crucial Role ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Site Specific ◽  
Lysine Residues

AbstractThe closely related acetyltransferases CBP and p300 are key regulators of gene expression in metazoans. CBP/p300 acetylate several specific lysine residues within nucleosomes, including histone H3 lysine 27 (H3K27), a hallmark of active enhancers and promoters. However, it has remained largely unclear how specificity of CBP/p300 towards H3K27 is achieved. Here we show that the TAZ2 domain of CBP is required for efficient acetylation of H3K27, while curbing activity towards other lysine residues within nucleosomes. We find that TAZ2 is a sequence-independent DNA binding module, promoting interaction between CBP and nucleosomes, thereby enhancing enzymatic activity and regulating substrate specificity of CBP. TAZ2 is further required to stabilize CBP binding to chromatin in mouse embryonic stem cells, facilitating specificity towards H3K27 and modulating gene expression. These findings reveal a crucial role of TAZ2 in regulating H3K27ac, while highlighting the importance of correct site-specific acetylation for proper regulation of gene expression.

scholarly journals H3K27me3 is dispensable for early differentiation but required to maintain differentiated cell identity

2020 ◽  
Author(s):  
Sara A. Miller ◽  
Manashree Damle ◽  
Robert E. Kingston
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Normal Development ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Gene Repression ◽  
Cellular Phenotype ◽  
Polycomb Repressive Complex 2 ◽  
Molecule Inhibitor

AbstractPolycomb repressive complex 2 (PRC2) catalyzes trimethylation of histone H3 on lysine 27 and is required for normal development of complex eukaryotes. The requirement for H3K27me3 in various aspects of mammalian differentiation is not clear. Though associated with repressed genes, the modification is not sufficient to induce gene repression, and in some instances is not required. To examine the role of the modification in mammalian differentiation, we blocked trimethylation of H3K27 with both a small molecule inhibitor, GSK343, and by introducing a point mutation into EZH2, the catalytic subunit of PRC2. We found that cells with substantively decreased H3K27 tri-methylation were able to differentiate, which contrasts with EZH2 null cells. Different PRC2 targets had varied requirements for H3K27me3 in repressive regulation with a subset that maintained normal levels of repression in the absence of methylation. The primary cellular phenotype when H3K27 tri-methylation was blocked was an inability of the altered cells to maintain a differentiated state when challenged. This phenotype was determined by H3K27me3 deposition both in embryonic stem cells and in the first four days of differentiation. H3K27 tri-methylation therefore was not necessary for formation of differentiated cell states but was required to maintain a stable differentiated state.

Cancer and Evolution

2006 ◽  
Vol 52 (3-4) ◽  
pp. 233-245 ◽  
Author(s):  
Walter. F. Bodmer
Keyword(s):  
Stem Cells ◽  
Germ Line ◽  
Evolutionary Process ◽  
Current Evidence ◽  
Benign Tumors ◽  
Proliferating Cells ◽  
Genetic Changes ◽  
Differentiated Cells ◽  
Selective Forces

Cancer mostly is a disease of old age. Evolutionary pressures have pushed the somatic "error rate", especially the mutation rate, down to a level where for most organisms cancer is no longer of any selective significance. This appears to be a by-product of the selection that gives rise to senescence, following the arguments of Medawar, Holliday, and Kirkwood. The development of a cancer is discussed from an evolutionary viewpoint, emphasising the role of selection versus mutation and the fact that each cancer is an independent evolutionary process. The nature of the selective advantages associated with the somatic genetic changes during a cancer's evolution can sometimes be inferred by reference to the known types of mutations found in cancers. Examples are given using colorectal cancer as a model. The major selective forces involve the balance between selection for increased growth rate and against apoptosis. There are strong arguments against the much discussed role of genomic instability as a requirement for cancer. Current evidence suggests that instability is a byproduct of selection against apoptosis. There is an important contrast between germ line and somatic changes, the former being the basis for inherited susceptibilities to cancer, while the latter are the fundamental changes that turn a normal cell into a cancer cell. Tissue stem cells, as in the colonic crypt, provide the source, through division and differentiation, of the differentiated cells in a crypt. Mathematical models can provide an explanation for how the balance in a crypt between stem cells, intermediate proliferating cells, and non-proliferating differentiated cells is maintained. Perturbations of the renewal parameters in the model can explain the evolution of benign tumors, namely polyps or adenomas, and the eventually exponential growth of cells resulting in a fully developed carcinoma. It seems probable that the origin of most carcinomas is in the intermediate proliferating cells, and that these are therefore the likely source of cancer stem cells.

scholarly journals Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation

2020 ◽  
Vol 117 (31) ◽  
pp. 18439-18447
Author(s):  
Wendan Ren ◽  
Huitao Fan ◽  
Sara A. Grimm ◽  
Yiran Guo ◽  
Jae Jin Kim ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Histone Modifications ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Genomic Stability ◽  
Epigenetic Modifications ◽  
Global Dna Methylation ◽  
Replication Foci ◽  
Direct Readout

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

Epigenetics in the heart: the role of histone modifications in cardiac remodelling

2013 ◽  
Vol 41 (3) ◽  
pp. 789-796 ◽  
Author(s):  
Asmita Tingare ◽  
Bernard Thienpont ◽  
H. Llewelyn Roderick
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Cardiac Development ◽  
Histone H3 ◽  
Cardiomyocyte Proliferation ◽  
Genome Wide ◽  
Pathological Hypertrophy ◽  
Number Of Genes ◽  
Recent Developments

Understanding the molecular mechanisms underlying cardiac development and growth has been a longstanding goal for developing therapies for cardiovascular disorders. The heart adapts to a rise in its required output by an increase in muscle mass and alteration in the expression of a large number of genes. However, persistent stress diminishes the plasticity of the heart, consequently resulting in its maladaptive growth, termed pathological hypertrophy. Recent developments suggest that the concomitant genome-wide remodelling of the gene expression programme is largely driven through epigenetic mechanisms such as post-translational histone modifications and DNA methylation. In the last few years, the distinct functions of histone modifications and of the enzymes catalysing their formation have begun to be elucidated in processes important for cardiac development, disease and cardiomyocyte proliferation. The present review explores how repressive histone modifications, in particular methylation of H3K9 (histone H3 Lys9), govern aspects of cardiac biology.

scholarly journals Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation

2020 ◽  
Author(s):  
Wendan Ren ◽  
Huitao Fan ◽  
Sara A Grimm ◽  
Yiran Guo ◽  
Jae Jin Kim ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Histone Modifications ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Genomic Stability ◽  
Epigenetic Modifications ◽  
Global Dna Methylation ◽  
Replication Foci ◽  
Direct Readout

ABSTRACTIn mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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