Silence of the genes — mechanisms of long-term repression

Lande-Diner, Laura; Cedar, Howard

doi:10.1038/nrg1639

Cited by 79 publications

(71 citation statements)

References 101 publications

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“…Transposon silencing, parental imprinting, X-chromosome inactivation and cell differentiation involve gene silencing through epigenetic mechanisms. 16 Similarly, somatic epimutations may play a role in many cancers. 17 Although the role of epigenetics in developmental plasticity has focused largely on parental imprinting, we suspect imprinting has other critical functions and is unlikely to be regulated within the normative range of developmental environments to affect metabolic regulation later in life, although it may play a role in more disruptive situationsFfor example, imprinting disorders such as the Weidemann-Beckwith syndrome are more common in the offspring following assisted reproductive techniques.…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

2008

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Although variation in individual lifestyle and genotype are important factors in explaining individual variation in the risk of developing obesity in an obesogenic environment, there is growing evidence that developmentally plastic processes also contribute. These effects are mediated at least in part through epigenetic processes. These developmental pathways do not directly cause obesity but rather alter the risk of an individual developing obesity later in life. At least two classes of developmental pathway are involved. The mismatch pathway involves the evolved adaptive responses of the developing organism to anticipated future adverse environments, which have maladaptive consequences if the environment is mismatched to that predicted. This pathway can be cued by prenatal undernutrition or stresses that lead the organism to forecast an adverse future environment and change its developmental trajectory accordingly. As a result, individuals develop with central and peripheral changes that increase their sensitivity to an obesogenic environment. It provides a model for how obesity emerges in populations in rapid transition, but also operates in developed countries. There is growing experimental evidence that this pathway can be manipulated by, for example, postnatal leptin exposure. Secondly, maternal diabetes, maternal obesity and infant overfeeding are associated with a greater risk of later obesity. Early life offers a potential point for preventative intervention.

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Section: Epigenetic Mechanismsmentioning

confidence: 99%

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

2008

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“…HP1 is a chromodomain protein that specifically recognizes trimethylated lysine 9 of histone H3, thereby favoring the assembly of heterochromatin [12][13][14]. Further heterochromatinization occurs by recruitment of DNA methyl transferases that will specifically methylate cytosine in the 5 position [15,16]. Together with these post-translational modifications, there is a progressive decrease in the accessibility of DNA to the transcription machinery and hence an increasing transcriptional silencing (Figure 1).…”

Section: The Hdac Familymentioning

confidence: 99%

“…The last member of class I, HDAC8, was recently found to be expressed in smooth muscle where it is required for muscle contractility [42]. This protein has also been linked to cancer since it is recruited by the leukemic INV [16] protein [43]; it regulates telomerase activity [44] and siRNAs targeting HDAC8 were shown to have antitumor effects in cell culture [45].…”

Section: Mammalian Deacetylasesmentioning

confidence: 99%

HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

et al. 2007

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Histone deacetylases (HDACs) and histone acetyl transferases (HATs) are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.

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“…7 Several lines of evidence suggest that replication timing is also strongly associated with local epigenetic features such as acetylation or methylation of specific histone residues and the presence or absence of certain regulatory protein(s) (reviewed in ref. 28). Therefore, if chromatin in the MHC is "poised" for rapid transcriptional activation, as suggested by the massive chromatin decondensation that occurs within minutes of exposure to IFNγ, 14 an "open" chromatin architecture might predispose to relatively early replication even in non-expressing cells.…”

Section: Discussionmentioning

confidence: 99%

Replication Timing Profile Reflects the Distinct Functional and Genomic Features of the MHC Class II Region

Takousis

Johonnett²,

Williamson³

et al. 2007

Cell Cycle

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The timing of DNA replication generally correlates with transcription, gene density and sequence composition. How is the timing affected if a genomic region has a combination of features that individually correlate with either early or late replication? The major histocompatibility complex (MHC) class II region is an AT-rich isochore that would be expected to replicate late, but it also contains coordinately regulated genes that are highly expressed in antigen-presenting cells and are strongly inducible in other cell types. Using cytological and biochemical assays, we find that the entire MHC replicates within the first half of S-phase, and that the class II region replicates slightly later than the adjacent regions irrespective of gene expression. These data suggest that despite ATrichness, an early-to-middle replication time in the class II region is defined by an open chromatin conformation that allows rapid transcriptional activation as a defence against pathogens.

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Silence of the genes — mechanisms of long-term repression

Cited by 79 publications

References 101 publications

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

Replication Timing Profile Reflects the Distinct Functional and Genomic Features of the MHC Class II Region

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