This study demonstrates that siRNA off-targets (e.g. 3'UTR off-targets), can be significantly reduced when cells are treated with a relatively low dose of siRNA (e.g. 1nM) that is sufficient to effectively silence the intended target.
siRNA off-target effects can be reduced at concentrations that match their individual potency.
Cell line
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Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.
Specimen part, Cell line
View SamplesWe used microarrays to detail the global program of gene expression underlying rRNA processing gene regulation during heat shock. PBF1 is YBL054W (TOD6) and PBF2 is YER088C (DOT6).
High-resolution DNA-binding specificity analysis of yeast transcription factors.
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View SamplesDendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function.
Temporal regulation of nuclear factor one occupancy by calcineurin/NFAT governs a voltage-sensitive developmental switch in late maturing neurons.
Specimen part
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Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
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CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
Specimen part
View SamplesNucleosome arrangement in promoter regions has been shown to play an important role in gene regulation. Genome wide studies in yeast, flies, worms, mammalian ES and transformed cell lines have found well positioned nucleosomes with an area of nucleosome depletion flanking transcription start sites. This Nucleosome arrangement has been shown to be dependent on sequence (cis-regulatory factors), DNA binding factors (trans-regulatory factors) and ATP-dependant chromatin modifiers. However, little is understood about how the nascent embryonic genome positions nucleosomes during development. This is particularly intriguing since the embryonic genome undergoes a whole scale rechromatinization event upon fusion of sperm and oocyte. Using four stages of early embryonic zebrafish development we map nucleosome positions at the promoter region of 34 zebrafish hox genes. We find that nucleosome arrangement at the hox promoters is a dynamic process which happens over several stages. We also find evidence that trans-regulatory factors play a greater role in nucleosome positioning over cis-regulatory elements. Finally we provide evidence that transcriptional activation is the driving force behind the arrangement of nucleosomes at the promoters of hox gene during early development.
Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.
Specimen part, Cell line
View SamplesThe transcriptional repressor BLIMP1 is a master regulator of B and T cell differentiation. To examine the role of BLIMP1 in innate immunity we used a conditional knockout (CKO) of Blimp1 in myeloid cells and found that Blimp1 CKO mice were protected from lethal infection induced by Listeria monocytogenes. Transcriptome analysis of Blimp1 CKO macrophages identified the murine chemokine (C-C motif) ligand 8, CCL8 as a direct target of Blimp1-mediated transcriptional repression in these cells. BLIMP1-deficient macrophages expressed elevated levels of Ccl8 and consequently Blimp1 CKO mice had higher levels of circulating CCL8 resulting in increased neutrophils in the peripheral blood, promoting a more aggressive anti-bacterial response. Mice lacking the Ccl8 gene were more susceptible to L. monocytogenes infection than wild type mice. While CCL8 failed to recruit neutrophils directly, it was chemotactic for / T cells and CCL8-responsive / T cells were enriched for IL-17F. Finally, CCL8-mediated enhanced clearance of L. monocytogenes was dependent on / T cells. Collectively, these data reveal an important role for BLIMP1 in modulating host-defenses by suppressing expression of the chemokine CCL8.
The transcriptional repressor BLIMP1 curbs host defenses by suppressing expression of the chemokine CCL8.
Specimen part
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Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
Time
View SamplesGene expression was compared from adult C. elegans after RNAi
No associated publication
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