title: Long noncoding RNAs with enhancer-like function in human cells.
abstract: While the long noncoding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to decreased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in activation of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Ulf Andersson
authors.initials: UA
authors.lastname: Ørom
authors.forename: Thomas
authors.initials: T
authors.lastname: Derrien
authors.forename: Malte
authors.initials: M
authors.lastname: Beringer
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Gumireddy
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gardini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussotti
authors.forename: Fan
authors.initials: F
authors.lastname: Lai
authors.forename: Matthias
authors.initials: M
authors.lastname: Zytnicki
authors.forename: Cedric
authors.initials: C
authors.lastname: Notredame
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigo
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D015894:Genome, Human; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors