Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster.
The ratio of noncoding to protein coding DNA rises with the complexity of the organism, culminating in nearly 99% of nonprotein coding DNA in humans. Nevertheless, a large portion of these regions is transcribed, creating the alleged paradox that noncoding RNA (ncRNA) represents the largest output of the human genome. Such a complex scenario may include epigenetic mechanisms where ncRNAs would be involved in chromatin regulation. We have investigated the intergenic, noncoding transcriptomes of mammalian HOX clusters. We show that "opposite strand transcription" from the intergenic spacer regions in the human HOXA cluster correlates with the activity state of adjacent HOXA genes. This noncoding transcription is regulated by the retinoic acid morphogen and follows the colinear activation pattern of the cluster. Opening of the cluster at sites of activation of intergenic transcripts is accompanied by changes in histone modifications and a loss of interaction with Polycomb group (PcG) repressive complexes. We propose that noncoding transcription is of fundamental importance for the opening and maintenance of the active state of HOX clusters.
Sessa
Luca
L
Dulbecco Telethon Institute, Naples, Italy.
Breiling
Achim
A
Lavorgna
Giovanni
G
Silvestri
Laura
L
Casari
Giorgio
G
Orlando
Valerio
V
D000818:Animals; D045744:Cell Line, Tumor; D019295:Computational Biology; D018899:CpG Islands; D021901:DNA, Intergenic; D044127:Epigenesis, Genetic; D020224:Expressed Sequence Tags; D005333:Fetus / Q000737:chemistry; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D051379:Mice; D005810:Multigene Family; D063146:Polycomb-Group Proteins; D012313:RNA / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D020218:Response Elements; D012984:Software; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D021901:DNA, Intergenic; D006657:Histones; D018398:Homeodomain Proteins; D063146:Polycomb-Group Proteins; D016372:RNA, Antisense; D022661:RNA, Untranslated; D012097:Repressor Proteins; C088144:HoxA protein; D014212:Tretinoin; D012313:RNA