Abstract:SUMMARYMuch of what we know about the role of epigenetics in the determination of phenotype has come from studies of inbred mice. Some unusual expression patterns arising from endogenous and transgenic murine alleles, such as the Agouti coat color alleles, have allowed the study of variegation, variable expressivity, transgenerational epigenetic inheritance, parent-of-origin effects, and position effects. These phenomena have taught us much about gene silencing and the probabilistic nature of epigenetic proces… Show more
“…X irradiation is much more likely than other commonly used mutagens to induce chromosomal rearrangements that can result in PEV. Similar mutations have been isolated from the mouse, in which variegating coat color indicates PEV (see Blewitt and Whitelaw 2013). For example, the insertion of an autosomal region carrying a fur color gene onto the X chromosome results in variable silencing of the allele (Russel and Bangham 1961;Cattanach 1961).…”
Section: Pev Heterochromatin Formation and Gene Silencing In Differmentioning
confidence: 83%
“…In Drosophila, virtually every gene that has been examined in an appropriate rearrangement has been shown to variegate, and rearrangements involving the pericentric heterochromatin of any chromosome can lead to PEV (Girton and Johansen, 2008). PEV has subsequently been observed in a variety of organisms, including yeasts (see Allshire and Ekwall 2014), flies, and mammals (see Blewitt and Whitelaw 2013;Brockdorff and Turner 2014), but has been used as a tool to study heterochromatin formation primarily in Drosophila.…”
“…X irradiation is much more likely than other commonly used mutagens to induce chromosomal rearrangements that can result in PEV. Similar mutations have been isolated from the mouse, in which variegating coat color indicates PEV (see Blewitt and Whitelaw 2013). For example, the insertion of an autosomal region carrying a fur color gene onto the X chromosome results in variable silencing of the allele (Russel and Bangham 1961;Cattanach 1961).…”
Section: Pev Heterochromatin Formation and Gene Silencing In Differmentioning
confidence: 83%
“…In Drosophila, virtually every gene that has been examined in an appropriate rearrangement has been shown to variegate, and rearrangements involving the pericentric heterochromatin of any chromosome can lead to PEV (Girton and Johansen, 2008). PEV has subsequently been observed in a variety of organisms, including yeasts (see Allshire and Ekwall 2014), flies, and mammals (see Blewitt and Whitelaw 2013;Brockdorff and Turner 2014), but has been used as a tool to study heterochromatin formation primarily in Drosophila.…”
“…The replacement of histones during sperm maturation by protamines and other proteins provides a potential means of erasing epigenetic information in the male germline. However, evidence for transgenerational inheritance (Rakyan and Whitelaw 2003; discussed in more detail in Blewitt and Whitelaw 2013), especially in animals that lack DNA methylation, raises the possibility that a subset of nucleosomal histones survive this transition and transmit epigenetic information. As already pointed out, this is just what occurs for CENP-A at centromeres (Palmer et al 1990), and it is possible that a small fraction of other variants, such as H3.3, remain with sperm for epigenetic inheritance of gene-expression information.…”
Section: Many Histones Have Evolved To More Tightly Package Dnamentioning
“…When some epigenetic marks are incompletely removed during gametogenesis, this can apparently lead to epigenetic inheritance through the germline, of which there are a number of examples now in mammals (e.g., see Fig. 6 in Blewitt andWhitelaw 2013 andChong andWhitelaw 2004), and this could potentially explain the transgenerational epigenetic inheritance of some metabolic phenotypes (FergusonSmith and Patti 2011). How widespread this phenomenon is and how many gene loci it involves needs to be established.…”
Section: Regulation Of Epigenetic Programming After Pgc Specificationmentioning
SUMMARYEpigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.
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