Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription.
Michael S WernerMatthew A SullivanRohan N ShahRangarajan D NadadurAdrian T GrzybowskiVasiliy GalatIvan P MoskowitzAlexander J RuthenburgPublished in: Nature structural & molecular biology (2017)
We recently described a new class of long noncoding RNAs (lncRNAs) that are distinguished by especially tight chromatin association and whose presence is strongly correlated to expression of nearby genes. Here, we examine the cis-enhancer mechanism of this class of chromatin-enriched RNA (cheRNA) across multiple human cell lines. cheRNAs are largely cell type specific and provide the most reliable chromatin signature to predict cis-gene transcription in every human cell type examined. Targeted depletion of three cheRNAs decreases expression of their neighboring genes, indicating potential co-activator function, and single-molecule fluorescence in situ hybridization (smFISH) of one cheRNA-distal target gene pair suggests a spatial overlap consistent with a role in chromosome looping. Additionally, the cheRNA HIDALGO stimulates the fetal hemoglobin subunit gamma 1 (HBG1) gene during erythroid differentiation by promoting contacts to a downstream enhancer. Our results suggest that multiple cheRNAs activate proximal lineage-specific gene transcription.
Keyphrases
- genome wide identification
- transcription factor
- genome wide
- single molecule
- copy number
- genome wide analysis
- dna methylation
- gene expression
- endothelial cells
- dna damage
- poor prognosis
- blood brain barrier
- immune response
- oxidative stress
- atomic force microscopy
- minimally invasive
- drug delivery
- quantum dots
- network analysis
- human health
- living cells
- nucleic acid
- bioinformatics analysis