Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Histone deacetylase inhibition of BT474

ABSTRACT: breast cancer cell line BT474 were treated with TSA or vehicle (DMSO) for 4 hours

ORGANISM(S): Homo sapiens

SUBMITTER: Tae Hoon Kim

PROVIDER: E-MTAB-666 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade.

Kim Y J YJ Greer C B CB Cecchini K R KR Harris L N LN Tuck D P DP Kim T H TH

Oncogene 20130225 23

Treatment with histone deacetylase inhibitors (HDACI) results in potent cytotoxicity of a variety of cancer cell types, and these drugs are used clinically to treat hematological tumors. They are known to repress the transcription of ERBB2 and many other oncogenes, but little is known about this mechanism. Using global run-on sequencing (GRO-seq) to measure nascent transcription, we find that HDACI cause transcriptional repression by blocking RNA polymerase II elongation. Our data show that HDAC ...[more]

PMID: 23435418

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Project description:Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.

Dataset Information

Histone deacetylase inhibition of BT474

Publications

HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade.

Similar Datasets

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