Expression of S-Phase long non-coding RNAs (SPEARs) exert a key transcriptional regulatory role through acH2A.Z activating mark deposition

The mechanisms by which epigenetic modifications are established at active genes remain elusive. The present data demonstrate that the appearance of a major epigenetic mark - the acetylated form of H2A.Z - is regulated by cell cycle-specific long noncoding RNAs encoded in regions adjacent to the promoters of active genes. These transcripts, termed Spears (S Phase EArly RNAs) are induced in early S phase: their expression precedes and then controls that of the downstream gene. Spears set the stage for the deposition of the acetylated form of histone H2A.Z by associating with the replacement histone H2A.Z and with the histone acetyl transferase Tip60,. This widespread bimodal interaction uncovers a novel RNA-mediated mechanism for the establishment of cell-specific epigenetic profiles and provides a potentially unifying mechanistic explanation for the accuracy and persistence of epigenetic marks on chromatin. Interaction between H2A.Z and A7:B16 Early RNAs; Interaction betweenTip60 and S-Phase Early RNAs; S-Phase Early RNAs and gene expression.