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SRP068046
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2000
Description
The euchromatin histone methyltransferase 2 (EHMT2, aka G9a) methylates histone H3K9 to repress gene expression, but it also acts as a coactivator for some nuclear receptors. The molecular mechanisms underlying this activation remain elusive. Here we show that G9a functions as a bona fide coactivator of the endogenous estrogen receptor a (ERa) in breast cancer cells in a histone methylation-independent manner. G9a dimethylates ERa protein at lysine 235 both in vitro and in cells. Dimethylation of ERaK235 (ERaK235me2) is recognized by the Tudor domain of PHF20, which in turn recruits the MOF histone acetyltransferase (HAT) complex to ERa target gene promoters to deposit histone H4K16 acetylation promoting active transcription. Together, our in vitro and in vivo data establish the molecular mechanism by which G9a functions as an ERa coactivator. Along with the PHF20/MOF complex, G9a links the crosstalk between ERa methylation and histone acetylation governing the epigenetic regulation of hormonal gene expression. Overall design: G9a KD RNA-seq and PHF20 KD RNA-seq with and without E2 treatment
Publication Title
G9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
We find that 499 genes are up-regulated and 457 are down-regulated in response to over-expression of JADE1, while 397 genes are up-regulated and 385 are down-regulated after HBO1 knock-down.
Publication Title
Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 4000
Description
RNA was sequenced from Disomic and Trisomic individuals for chromosome 21 to identify consistent changes in gene expression across individuals Overall design: Cells were cultured at subconfluency and RNA harvested for sequencing
Publication Title
Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase.
Sample Metadata Fields
Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from triplicate log-phase cultures of BY4741 (WT) transformed with pRS313-HA3-SSN6 and taf14D transformed with pRS313-HA3-SSN6 (empty vector), full-length pRS313-TAF14-HA3-SSN6, or pRS313-taf14W81A-HA3-SSN6 cultured in synthetic complete media lacking histidine. Overall design: Examination of changes in gene expression when the YEATS domain of Taf14 is mutated so it cannot bind acetyl-H3.
Publication Title
Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TCL1 is an an oncogene and transgenic (Tg) mice expressing TCL1 specifically in B-cells are well-characterized models for chronic lymphocytic leukemia. On the contrary, PTPROt is a phosphatase with tumor suppressor characteristics in many cancers including leukemia. Our hypothesis was that transgenic expression of PTPROt in the B-cells of TCL1 Tg mice will alleviate disease phenotype and allow the study of the in vivo mechanism of action of PTPROt. To test this we have generated Tg mice with B-cell specific expression of PTPROt and crossed these mice with the TCL1 Tg mice.
Publication Title
PTPROt-mediated regulation of p53/Foxm1 suppresses leukemic phenotype in a CLL mouse model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 81 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcript data from livers from fasted-state BXD strains on chow or high fat diet
Publication Title
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88x10-2 5.02x10-9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 involved in DNA repair are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show that cellular defences against DNA damage may take part in the pathogenesis of NSCL/P, in accordance with the hypothesis of aetiological overlap between this malformation and cancer. These results provide more information regarding the aetiology of NSCL/P and have the potential tocan potentially assist incontribute to the development of future preventive strategies.
Publication Title
Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 910 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA profile for timecourse of neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124).
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA interacting protein immunoprecipitation with AGO2 for miR-124 target enrichment from neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124) and subsequent sequencing.
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples