Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profile of the human beta-globin locus.
Several lines of evidence have established strong links between transcriptional activity and specific post-translation modifications of histones. Here we show using RNA FISH that in erythroid cells, intergenic transcription in the human beta-globin locus occurs over a region of greater than 250 kb including several genes in the nearby olfactory receptor gene cluster. This entire region is transcribed during S phase of the cell cycle. However, within this region there are approximately 20 kb sub-domains of high intergenic transcription that occurs outside of S phase. These sub-domains are developmentally regulated and enriched with high levels of active modifications primarily to histone H3. The sub-domains correspond to the beta-globin locus control region, which is active at all developmental stages in erythroid cells, and the region flanking the developmentally regulated, active globin genes. These results correlate high levels of non-S phase intergenic transcription with domain-wide active histone modifications to histone H3.
Miles
Joanne
J
Laboratory of Chromatin and Gene Expression, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
Mitchell
Jennifer A
JA
Chakalova
Lyubomira
L
Goyenechea
Beatriz
B
Osborne
Cameron S
CS
O'Neill
Laura
L
Tanimoto
Keiji
K
Engel
James Douglas
JD
Fraser
Peter
P
D000328:Adult; D000740:Anemia / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002874:Chromosome Mapping / Q000379:methods; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012313:RNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000502:physiology; D012903:Smell / Q000235:genetics; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D055544:beta-Globins; D012313:RNA