Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Lu, Brett Y.; Bishop, Clifton P.; Eissenberg, Joel C.

doi:10.1002/j.1460-2075.1996.tb00474.x

Cited by 85 publications

(96 citation statements)

References 60 publications

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“…In the hybrid genotypes, the expression of SXL is abnormal, but still distinctive between the sexes. The respective patterns for the D. simulans females by the D. melanogaster cross were confirmed by using a lacZ-marked Y chromosome stock (Lu et al 1996) and crossing it with the same D. simulans stock, followed by staining for SXL and lacZ.…”

Section: Methodsmentioning

confidence: 86%

Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids

Bhadra

Birchler

2006

Genetics

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A major model system for the study of evolutionary divergence between closely related species has been the unisexual lethality resulting from reciprocal crosses of Drosophila melanogaster and D. simulans. Sex-lethal (Sxl), a critical gene for sex determination, is misregulated in these hybrids. In hybrid males from D. melanogaster mothers, there is an abnormal expression of Sxl and a failure of localization of the male-specific lethal (MSL) complex to the X chromosome, which causes changes in gene expression. Introduction of a Sxl mutation into this hybrid genotype will allow expression of the MSL complex but there is no sequestration to the X chromosome. Lethal hybrid rescue (Lhr), which allows hybrid males from this cross to survive, corrects the SXL and MSL defects. The reciprocal cross of D. simulans mothers by D. melanogaster males exhibits underexpression of Sxl in embryos.

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Section: Methodsmentioning

confidence: 86%

Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids

Bhadra

Birchler

2006

Genetics

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“…Natural loss, then, and the resultant shift in heterochromatin/euchromatin balance may provide a simple explanation for the progressive loss of heterochromatic silencing in differentiating cells (46) and an explanation for why some epigenetic states are clonally inherited. We envision that cells initially contain large rDNA arrays, which permits heterochromatin formation.…”

Section: Discussionmentioning

confidence: 99%

“…This gives rise to stable decisions in the ''deciding'' and any progeny cells, resulting in the familiar patches of expressing cells and non-expressing cells which reflect cell lineage (46). This view predicts that every set of genes linked to a heterochromatic/euchromatic junction is independent, and that decisions made at one junction influence closely-linked genes, but not genes near other junctions.…”

mentioning

confidence: 99%

Ribosomal DNA contributes to global chromatin regulation

Paredes

Maggert

2009

Proc. Natl. Acad. Sci. U.S.A.

142

144

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The 35S ribosomal RNA genes (rDNA) are organized as repeated arrays in many organisms. Epigenetic regulation of transcription of the rRNA results in only a subset of copies being transcribed, making rDNA an important model for understanding epigenetic chromatin modification. We have created an allelic series of deletions within the rDNA array of the Drosophila Y chromosome that affect nucleolus size and morphology, but do not limit steady-state rRNA concentrations. These rDNA deletions result in reduced heterochromatin-induced gene silencing elsewhere in the genome, and the extent of the rDNA deletion correlates with the loss of silencing. Consistent with this, chromosomes isolated from strains mutated in genes required for proper heterochromatin formation have very small rDNA arrays, reinforcing the connection between heterochromatin and the rDNA. In wild-type cells, which undergo spontaneous natural rDNA loss, we observed the same correlation between loss of rDNA and loss of heterochromatin-induced silencing, showing that the volatility of rDNA arrays may epigenetically influence gene expression through normal development and differentiation. We propose that the rDNA contributes to a balance between heterochromatin and euchromatin in the nucleus, and alterations in rDNA-induced or natural-affect this balance.Drosophila ͉ epigenetics ͉ heterochromatin ͉ nucleolus ͉ rDNA C hromatin within the nucleus is divided into cytologically heterochromatic and euchromatic compartments (1). This division reflects very different functional influences on gene expression (2). Many genes adopt more ''heterochromatin-like'' features when inactivated, including cytological appearance and association with specific proteins or post-translational modifications. This has led to hypotheses that similar mechanisms regulate facultatively inactivated genes or chromosomes, constitutively heterochromatic regions of the genome, and developmentally repressed genes (3). Understanding the interplay between heterochromatin and euchromatin, then, is fundamental in understanding the control of epigenetic regulation of the genome.Gene products involved in heterochromatin formation have been primarily identified by observing the effect of mutations on position effect variegation (PEV), which manifests as mosaic expression of a gene placed in a heterochromatic context. Many of these mutations act dominantly, thus the genes are thought to encode dosesensitive components of heterochromatin (4). Equally important to models of heterochromatin formation is the observation that the amount of constitutive heterochromatin in the nucleus affects heterochromatin-induced PEV at unlinked genes (5). In this model, gene products act as a ''source'' of heterochromatin forming potential, and DNA sequences destined to be heterochromatic as a ''sink.'' A balance is normally maintained between gene products and target DNA in the genome, although no proposed mechanism satisfactorily accounts for how this balance is maintained during division, determination, and differe...

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“…The work of Lu et al (1996) and Weiler and Wakimoto (1998) has shown that silencing occurs early in development and that there is a relaxation of silencing with terminal differentiation. While these studies agree, a more recent study emphasized the importance of the strength of the expression of the target gene in counteracting its silencing (Ahmad and Henikoff 2001).…”

Section: Discussionmentioning

confidence: 99%

“…One factor that differed between these promoters was the developmental time of expression. This is intriguing, as studies on cis-acting PEV have shown that development plays a role in silencing (Lu et al 1996;Weiler and Wakimoto 1998;Ahmad and Henikoff 2001). The studies on cisacting PEV and trans-inactivation have provided intriguing results and suggest additional questions to be addressed.…”

Section: P Osition-effect Variegation (Pev) Is the Silenc-mentioning

confidence: 99%

Interplay of Developmentally Regulated Gene Expression and Heterochromatic Silencing in Trans in Drosophila

Sage¹,

Csink

2008

Genetics

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The brown Dominant (bw D ) allele of Drosophila contains a heterochromatic block that causes the locus to interact with centric heterochromatin. This association silences bw 1 in heterozygotes (trans-inactivation) and is dependent on nuclear organizational changes later in development, suggesting that transinactivation may not be possible until later in development. To study this, a P element containing an upstream activating sequence (UAS)-GFP reporter was inserted 5 kb from the bw D insertion site. Seven different GAL4 driver lines were used and GFP fluorescence was compared in the presence or the absence of bw D . We measured silencing in different tissues and stages of development and found variable silencing of GFP expression driven by the same driver. When UAS-GFP was not expressed until differentiation in the eye imaginal disc it was more easily trans-inactivated than when it was expressed earlier in undifferentiated cells. In contrast to some studies by other workers on silencing in cis, we did not find consistent correlation of silencing with level of expression or evidence of relaxation of silencing with terminal differentiation. We suggest that such contrasting results may be attributed to a potentially different role played by nuclear organization in cis and trans position-effect variegation. P OSITION-EFFECT variegation (PEV) is the silencing of gene expression by nearby heterochromatin. The phenomenon was first described in Drosophila and has long served as a model for the downregulation of expression by chromatin compaction and changes in higher-order chromatin organization. Classic cis-acting PEV results from a chromosomal break and rejoining that juxtaposes a euchromatic gene and a block of constitutive heterochromatin. In contrast to earlier ideas concerning the continuous, straightforward linear spreading of the silent state, a collection of recent studies have found that the phenomenon is more complex. Many factors influence the susceptibility or resistance of a gene to silencing by heterochromatin in cis, such as the size, composition, and distance of the heterochromatic block and, most importantly, the specifics of the expression properties of the gene being silenced (for review see Talbert and Henikoff 2006).While these studies addressed cis-acting PEV, there is a similar, related phenomenon in flies of silencing by heterochromatin in trans. In trans-acting PEV, or ''transinactivation,'' the block of heterochromatin and the silenced gene are not necessarily on the same DNA molecule, but are brought close to each other within the space of the interphase nucleus. It is probable that this type of PEV is similar to downregulation of a number of normal genes in higher eukaryotes, as increasing evidence finds developmentally silenced loci that move into association with large blocks of heterochromatin (for example, see Su et al. 2004). A well-studied example of trans-inactivation is the brown Dominant (bw D

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Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Cited by 85 publications

References 60 publications

Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids

Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids

Ribosomal DNA contributes to global chromatin regulation

Interplay of Developmentally Regulated Gene Expression and Heterochromatic Silencing in Trans in Drosophila

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