Molecular Development - Epigenetics: Difference between revisions

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| DNA Methylation, young and old monozygous twins.<ref><pubmed>16009939</pubmed></ref>
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==Developmental Methylation changes==
Within the embryonic genome DNA methylation occurs at regions of cytosine residues followed by guanines (CpG) and is a main epigenetic mechanism regulating early gene expression and later genomic imprinting, see review.<ref><pubmed>20236475</pubmed></ref> There are extensive changes in DNA methylation state that occur during development and relate to imprinted genes, the total number of genes imprinted in currently unknown, with 100 identified imprinted genes in the mouse and about 50 known in the human. This imprinting will also differ between the embryo and the placenta.<ref name="PMID20617174"><pubmed>20617174</pubmed></ref>
Overall a developmental demethylation is followed by an eventual remethylation of about 70% of all CpGs, except for the primordial germ cell population. The primordial germ cells will form the germ line cell population in the embryo gonad. These cells appear to undergo epigenetic reprogramming through an independent genome-wide of erasure of imprints and epimutations through cytidine deaminases. (Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency.<ref><pubmed>20098412</pubmed></ref>
The zygote initially has a male and female pronucleus that will fuse to form the diploid nucleus. Each of the male and female pronuclei have different patterns of methylation and undergo different demethylation processes. The male pronucleus undergoes an extensive loss of DNA methylation, with imprinted genes resisting this process. The female pronucleus has less active demethylation requiring several mitotic rounds to complete this process.<ref><pubmed>20236475</pubmed></ref>


==Potential Imprinted Genes==
==Potential Imprinted Genes==

Revision as of 16:12, 4 December 2010

Introduction

Epigenetics mechanisms[1]

In terms of molecular mechanisms, the field of epigenetics has begun to florish with some recent important findings. Epigenetics as the name implies, is the inheritance mechanisms that lie outside the DNA sequence of our genes. One of the initial discoveries was the effects of DNA methylation upon gene expression and then modifications of nucleosomal histones. This DNA methylation, usually associated with 5-methylcytosine (m5C), leads to transcriptional silencing in vertebrates. Recently the term “methylome” has been coined to refer to the methylation profile of the whole genome.

Molecular mechanisms of development is an exciting area and requires a variety of different skills. This page introduces only a few examples and should give you a feel for the topic. Note that each section of system notes has a page covering molecular development in that system.

Molecular Links: molecular | genetics | epigenetics | mitosis | meiosis | X Inactivation | Signaling | Factors | Mouse Knockout | microRNA | Mechanisms | Developmental Enhancers | Protein | Genetic Abnormal | Category:Molecular

Some Recent Findings

  • Epigenetics 2010 [2] "This collection brings together twenty Research Articles published in five PLoS journals in the area of epigenetics during 2010, along with a Research in Translation article and two Primers. They reflect a range of model systems and organisms, and variously offer phenotypic, mechanistic, and chromatin-based insights."
  • Epigenetic memory in induced pluripotent stem cells. [3] "Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment." (More? Stem Cells)
  • NIH Roadmap Epigenomics Program

DNA Methylation Changes with Age

Epigenetics - monozygous twins.jpg
DNA Methylation, young and old monozygous twins.[4]

Developmental Methylation changes

Within the embryonic genome DNA methylation occurs at regions of cytosine residues followed by guanines (CpG) and is a main epigenetic mechanism regulating early gene expression and later genomic imprinting, see review.[5] There are extensive changes in DNA methylation state that occur during development and relate to imprinted genes, the total number of genes imprinted in currently unknown, with 100 identified imprinted genes in the mouse and about 50 known in the human. This imprinting will also differ between the embryo and the placenta.[6]

Overall a developmental demethylation is followed by an eventual remethylation of about 70% of all CpGs, except for the primordial germ cell population. The primordial germ cells will form the germ line cell population in the embryo gonad. These cells appear to undergo epigenetic reprogramming through an independent genome-wide of erasure of imprints and epimutations through cytidine deaminases. (Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency.[7]

The zygote initially has a male and female pronucleus that will fuse to form the diploid nucleus. Each of the male and female pronuclei have different patterns of methylation and undergo different demethylation processes. The male pronucleus undergoes an extensive loss of DNA methylation, with imprinted genes resisting this process. The female pronucleus has less active demethylation requiring several mitotic rounds to complete this process.[8]


Potential Imprinted Genes

Placenta potential imprinted genes.png Maternal and paternal resource allocation.png
Placenta potential imprinted genes[6] Maternal and paternal resource allocation[6]

Activation-Induced cytidine Deaminase

Mammalian active DNA demethylation[9]

Activation-Induced cytidine Deaminase (AID) is an enzyme required for demethylation (removal of CpG methylation). Within the genome, DNA methylation is associated with epigenetic mechanisms and occurs at cytosine residues that are followed by guanines.[9] This enzyme is also found expressed in primordial germ cells.

Links: Primordial Germ Cell Development


References

  1. <pubmed>16688142</pubmed>
  2. PLoS Collection - Epigenetics 2010
  3. <pubmed>20644535</pubmed>
  4. <pubmed>16009939</pubmed>
  5. <pubmed>20236475</pubmed>
  6. 6.0 6.1 6.2 <pubmed>20617174</pubmed>
  7. <pubmed>20098412</pubmed>
  8. <pubmed>20236475</pubmed>
  9. 9.0 9.1 <pubmed>20236475</pubmed>

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June 2010 "epigenetics" - All (37097) Review (6256) Free Full Text (15778)


Search Pubmed Now: epigenetics


Glossary Links

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Cite this page: Hill, M.A. (2024, March 29) Embryology Molecular Development - Epigenetics. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Molecular_Development_-_Epigenetics

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