The human genome contains thousands of long noncoding RNAs (ncRNAs) transcribed 
from diverse genomic locations. A large set of long ncRNAs is transcribed 
independent of protein-coding genes. We have used the GENCODE annotation of the 
human genome to identify 3019 long ncRNAs expressed in various human cell lines 
and tissue. This set of long ncRNAs responds to differentiation signals in 
primary human keratinocytes and is coexpressed with important regulators of 
keratinocyte development. Depletion of a number of these long ncRNAs leads to 
the repression of specific genes in their surrounding locus, supportive of an 
activating function for ncRNAs. Using reporter assays, we confirmed such 
activating function and show that such transcriptional enhancement is mediated 
through the long ncRNA transcripts. Our studies show that long ncRNAs exhibit 
functions similar to classically defined enhancers, through an RNA-dependent 
mechanism.