RNA expression was measured by RNA-seq in Drosophila ML-DmBG3-c2 cells depleted for proteins involved in sister chromatid cohesion, and in developing third instar wing discs with or withough brca2 gene mutations Overall design: RNA expression in depleted cells was compared to mock treated cells and RNA expression in wing discs from brca2 mutant Drosophila was compared to expression in wing discs without brca2 mutations This series includes mock RNAi treated samples re-used from GSE100547.
Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function.
Specimen part, Cell line, Subject
View SamplesRNA expression was measured using RNA-seq Overall design: RNA levels in Mock-treated control Drosophila cells were compared to RNA levels in cells RNAi depleted for Ph, Sce, and Pc
Polycomb repressive complex 1 modifies transcription of active genes.
Subject
View SamplesRNA nascent transcription was measured using NT-seq Overall design: RNA nascent transcript levels in Mock-treated control Drosophila cells were compared to those in cells RNAi depleted for Ph and Sce
Polycomb repressive complex 1 modifies transcription of active genes.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cohesin and polycomb proteins functionally interact to control transcription at silenced and active genes.
Sex, Specimen part
View SamplesCohesin is crucial for proper chromosome segregation, but also regulates gene transcription and organism development by poorly understood mechanisms. We find that in Drosophila, cohesin functionally interacts with Polycomb group (PcG) silencing proteins at both silenced and active genes. Cohesin unexpectedly facilitates binding of Polycomb Repressive Complex 1 (PRC1) to many active genes. In contrast, cohesin and PRC1 binding are mutually antagonistic at silenced genes. PRC1 depletion decreases phosphorylated RNA polymerase and mRNA at many active genes, but increases them at silenced genes. Cohesin also facilitates long-range interactions between Polycomb Response Elements in the invected-engrailed gene complex where it represses transcription. These multiple distinct cohesin-PcG interactions reveal a previously unrecognized role for PRC1 in facilitating productive gene transcription, and provide new insights into how cohesin and PRC1 control development.
Cohesin and polycomb proteins functionally interact to control transcription at silenced and active genes.
Sex
View SamplesRad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21.
Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved.
Specimen part, Time
View SamplesEffects of Nipped-B and Rad21 sister chromatid cohesin proteins on gene expression data in ML-DmBG3 cells derived from Drosophila melanogaster larval central nervous system
Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.
Time
View SamplesCohesin is a well-known mediator of sister chromatid cohesion, but it also influences gene expression and development. These non-canonical roles of cohesin are not well understood, but are vital: gene expression and development are altered by modest changes in cohesin function that do not disrupt chromatid cohesion. To clarify cohesin’s roles in transcription, we measured how cohesin controls RNA polymerase II (Pol II) activity by genome-wide chromatin immunoprecipitation and precision global run-on sequencing. On average, cohesin-binding genes have more transcriptionally active Pol II and promoter-proximal Pol II pausing than non-binding genes, and are more efficient, producing higher steady state levels of mRNA per transcribing Pol II complex. Cohesin depletion frequently increases pausing at cohesin-binding genes, indicating that cohesin often facilitates transition of paused Pol II to elongation. In many cases this likely reflects a role for cohesin in transcriptional enhancer function. Strikingly, more than 95% of predicted extragenic enhancers bind cohesin, and cohesin depletion can reduce their association with Pol II, indicating that cohesin facilitates enhancer-promoter contact. Cohesin directly promotes transcription of the myc gene, and cohesin depletion reduces Pol II activity at most Myc target genes. The multiple transcriptional roles of cohesin revealed by these studies likely underlie the growth and developmental deficits caused by minor changes in cohesin activity. Overall design: The PRO-seq method was used to measure transcriptionally engaged Pol II genome-wide in two replicates each of mock RNAi-treated, Nipped-B RNAi-treated, and Rad21 RNAi-treated ML-DmBG3-c2 cells.
Genome-wide control of RNA polymerase II activity by cohesin.
Sex, Specimen part, Treatment, Subject
View SamplesCHOPS syndrome is caused by germline gain-of-function mutations of AFF4. Cornelia de Lange syndrome is caused by germline mutations of cohesin loading factors or cohesin complex genes such as NIPBL, SMC1A, SMC3 and HDAC8. There are many overlapping clinical features exist between CHOPS syndrome and Cornelia de Lange syndrome. To identified commonly dysregulated genes in CHOPS syndrome and Cornelia de Lange syndrome, we perfomred side-by-side transcriptome comparison between CHOPS syndrome and Cornelia de Lange syndrome.
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Specimen part, Disease, Disease stage
View SamplesAFF4 is a component of super elongation complex (SEC), which plays an important role in mobilizing paused RNA polymerase II at gene promoter regions. Using exome sequenging, we have identified a novel genetic disorder caused by missense mutations in AFF4. We propose CHOPS syndrome as a name for this new diagnosis. To evaluate the effect of identified missense mutations of AFF4, utilizing patient derived skin fibroblast cell lines, the gene expression analysis was perfomred.
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Specimen part, Disease, Disease stage
View Samples