Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription

Michael S. Werner, Matthew A. Sullivan, Rohan N. Shah, Rangarajan D. Nadadur, Adrian T. Grzybowski, Vasiliy Galat, Ivan P. Moskowitz, Alexander J. Ruthenburg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)596-603
Number of pages8
JournalNature Structural and Molecular Biology
Volume24
Issue number7
DOIs
StatePublished - Jul 1 2017

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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