Project description:Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states.
Project description:This dataset contains whole-genome RNA sequencing results from cortical neuronal cultures and serves as the basis for characterization of extra-coding RNA species from neuronal systems. This experiment contains six biological samples, each of which underwent PolyA+ and PolyA- RNA-seq. Samples were either unstimulated (i.e., treated with media alone; samples V1 and V2), stimulated with 25mM potassium chloride for 1hr (K1, K2) or inactivated with tetrodotoxin for 1hr (T1, T2). Datasets were obtained using RNA-seq from PolyA+ fractions or PolyA- fractions of RNA. PolyA- fractions are denoted "ec". Thus, 12 samples are listed here due to the difference in RNA library preparation.
Project description:This dataset contains whole-genome MBD (methylbinding domain) sequencing results from cortical neuronal cultures and serves as the basis for characterization of DNA methylation profiles from neuronal systems. This experiment contains three sequencing datasets from 2 biological samples. Two datasets originate from samples that underwent MBD-capture prior to whole-genome sequencing. A third dataset contains non-MBD-captured genomic DNA as a control.
Project description:This dataset contains whole-genome MBD (methylbinding domain) sequencing results from cortical neuronal cultures and serves as the basis for characterization of DNA methylation profiles from neuronal systems.
Project description:This dataset contains whole-genome RNA sequencing results from cortical neuronal cultures and serves as the basis for characterization of extra-coding RNA species from neuronal systems.
Project description:The cancer epigenome exhibits global loss of DNA methylation, which contributes to genomic instability and aberrant gene expression by mechanisms that are yet to be fully elucidated. We previously discovered over 3300 long non-coding (lnc)RNAs in human cells and demonstrated that specific lncRNAs regulate gene expression via interactions with chromatin-modifying complexes. Here, we tested whether lncRNAs could also associate with DNA methyltransferases to regulate DNA methylation and gene expression. Using RIP-seq, we identified a subset of lncRNAs that interact with the DNA methyltransferase DNMT1 in a colon cancer cell line, HCT116. One lncRNA, TCONS_00023265, which we named DACOR1 (DNMT1-associated Colon Cancer Repressed lncRNA 1), shows high, tissue-specific expression in the normal colon (including colon crypts) but was repressed in a panel of colon tumors and patient-derived colon cancer cell lines. We identified the genomic occupancy sites of DACOR1, which we found to significantly overlap with known differentially methylated regions (DMRs) in colon tumors. Induction of DACOR1 in colon cancer cell lines significantly reduced their ability to form colonies in vitro, suggesting a growth suppressor function. Consistent with the observed phenotype, induction of DACOR1 led to the activation of tumor-suppressor pathways and attenuation of cancer-associated metabolic pathways. Notably, DACOR1 induction resulted in down-regulation of Cystathionine ?-synthase, which is known to lead to increased levels of S-adenosyl methionine-the key methyl donor for DNA methylation. Collectively, our results demonstrate that deregulation of DNMT1-associated lncRNAs contributes to aberrant DNA methylation and gene expression during colon tumorigenesis.