Genome-wide Mapping of in Vivo Targets of the Drosophila Transcription Factor Krüppel

Matyash, Alexey; Chung, Ho‐Ryun; Jäckle, Herbert

doi:10.1074/jbc.m403345200

Cited by 14 publications

(14 citation statements)

References 63 publications

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“…A mutant in VGlut, implicated in energy transmission, synaptic activity, and transmembrane transport (67,68), also showed a reduced RCH response, which is consistent with the importance of membrane fluidity, cellular exchange, and energetics (40,41,44,69). In addition, a mutant in a transcription factor-binding gene involved in the significantly enriched function of transcription (CG32111) (70) significantly increased the degree of short-term plasticity after RCH treatment in both developmentally acclimated individuals reared at 18°C and individuals reared at 25°C.…”

Section: Rch At 25mentioning

confidence: 58%

Constraints, independence, and evolution of thermal plasticity: Probing genetic architecture of long- and short-term thermal acclimation

Gerken

Eller

Hahn

et al. 2015

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

139

196

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Seasonal and daily thermal variation can limit species distributions because of physiological tolerances. Low temperatures are particularly challenging for ectotherms, which use both basal thermotolerance and acclimation, an adaptive plastic response, to mitigate thermal stress. Both basal thermotolerance and acclimation are thought to be important for local adaptation and persistence in the face of climate change. However, the evolutionary independence of basal and plastic tolerances remains unclear. Acclimation can occur over longer (seasonal) or shorter (hours to days) time scales, and the degree of mechanistic overlap is unresolved. Using a midlatitude population of Drosophila melanogaster, we show substantial heritable variation in both short-and long-term acclimation. Rapid cold hardening (short-term plasticity) and developmental acclimation (long-term plasticity) are positively correlated, suggesting shared mechanisms. However, there are independent components of these traits, because developmentally acclimated flies respond positively to short-term acclimation. A strong negative correlation between basal cold tolerance and developmental acclimation suggests that basal cold tolerance may constrain developmental acclimation, whereas a weaker negative correlation between basal cold tolerance and short-term acclimation suggests less constraint. Using genome-wide association mapping, we show the genetic architecture of rapid cold hardening and developmental acclimation responses are nonoverlapping at the SNP and corresponding gene level. However, genes associated with each trait share functional similarities, including genes involved in apoptosis and autophagy, cytoskeletal and membrane structural components, and ion binding and transport. These results indicate substantial opportunity for short-term and long-term acclimation responses to evolve separately from each other and for short-term acclimation to evolve separately from basal thermotolerance.

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Section: Rch At 25mentioning

confidence: 58%

Constraints, independence, and evolution of thermal plasticity: Probing genetic architecture of long- and short-term thermal acclimation

Gerken

Eller

Hahn

et al. 2015

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

139

196

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“…Whole Mount in Situ Hybridization and Antibody StaininglacZ and eve expression were examined by in situ hybridization to whole mount preparations using antisense RNA probes as described (14). Kr expression was monitored by staining embryos with rabbit-raised anti-Kr antiserum followed by staining with goat anti-rabbit Cy2-conjugated fluorescent antibody (Dianova).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, ectopic expression of Kr in imaginal eye discs interferes with their normal development by causing an Irregular facet gain-offunction phenotype (12,13). The available evidence suggests that Kr acts mainly as a transcriptional repressor (14 -18) and is likely to control several hundred target genes (14,19). However, the mechanism of Kr-dependent transcriptional repression is still not fully understood.…”

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confidence: 99%

SAP18 Promotes Krüppel-dependent Transcriptional Repression by Enhancer-specific Histone Deacetylation

Matyash

Singh

Hanes

et al. 2009

Journal of Biological Chemistry

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Body pattern formation during early embryogenesis of Drosophila melanogaster relies on a zygotic cascade of spatially restricted transcription factor activities. The gap gene Krüppel ranks at the top level of this cascade. It encodes a C2H2 zinc finger protein that interacts directly with cis-acting stripe enhancer elements of pair rule genes, such as even skipped and hairy, at the next level of the gene hierarchy. Krüppel mediates their transcriptional repression by direct association with the corepressor Drosophila C terminus-binding protein (dCtBP). However, for some Krüppel target genes, deletion of the dCtBPbinding sites does not abolish repression, implying a dCtBPindependent mode of repression. We identified Krüppel-binding proteins by mass spectrometry and found that SAP18 can both associate with Krüppel and support Krüppel-dependent repression. Genetic interaction studies combined with pharmacological and biochemical approaches suggest a site-specific mechanism of Krüppel-dependent gene silencing. The results suggest that Krüppel tethers the SAP18 bound histone deacetylase complex 1 at distinct enhancer elements, which causes repression via histone H3 deacetylation.

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“…Thus, in silico targets need to be validated in an in vivo context where the recognition of DNA sequences by a given transcription factor (TF) is influenced by chromatin structure and interacting cofactors. The genomewide repertoire of motifs to which TFs bind in vivo can be revealed by formaldehyde cross-linking and chromatin immunoprecipitation (X-ChIP) using factor-specific antibodies (12)(13)(14). However, the X-ChIP-based approaches (12)(13)(14) are time-consuming because they involve cloning, sequencing, and mapping of immunoprecipitated DNA fragments.…”

mentioning

confidence: 99%

“…The genomewide repertoire of motifs to which TFs bind in vivo can be revealed by formaldehyde cross-linking and chromatin immunoprecipitation (X-ChIP) using factor-specific antibodies (12)(13)(14). However, the X-ChIP-based approaches (12)(13)(14) are time-consuming because they involve cloning, sequencing, and mapping of immunoprecipitated DNA fragments. Easier access to CRMs is expected to be achieved by combining X-ChIP with genomic microarrays (ChIPchip strategy).…”

mentioning

confidence: 99%

Mapping Dmef2-binding regulatory modules by using a ChIP-enriched in silico targets approach

Junion

Jagla

Duplant

et al. 2005

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

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Mapping the regulatory modules to which transcription factors bind in vivo is a key step toward understanding of global gene expression programs. We have developed a chromatin immunoprecipitation (ChIP)-chip strategy for identifying factor-specific regulatory regions acting in vivo. This method, called the ChIPenriched in silico targets (ChEST) approach, combines immunoprecipitation of cross-linked protein-DNA complexes (X-ChIP) with in silico prediction of targets and generation of computed DNA microarrays. We report the use of ChEST in Drosophila to identify several previously unknown targets of myocyte enhancer factor 2 (MEF2), a key regulator of myogenic differentiation. Our approach was validated by demonstrating that the identified sequences act as enhancers in vivo and are able to drive reporter gene expression specifically in MEF2-positive muscle cells. Presented here, the ChEST strategy was originally designed to identify regulatory modules in Drosophila, but it can be adapted for any sequenced and annotated genome.Dmef2 ͉ transcription factor

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Genome-wide Mapping of in Vivo Targets of the Drosophila Transcription Factor Krüppel

Cited by 14 publications

References 63 publications

Constraints, independence, and evolution of thermal plasticity: Probing genetic architecture of long- and short-term thermal acclimation

Constraints, independence, and evolution of thermal plasticity: Probing genetic architecture of long- and short-term thermal acclimation

SAP18 Promotes Krüppel-dependent Transcriptional Repression by Enhancer-specific Histone Deacetylation

Mapping Dmef2-binding regulatory modules by using a ChIP-enriched in silico targets approach

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