DNA replication timing of the human beta-globin domain is controlled by histone modification at the origin.
The human beta-globin genes constitute a large chromosomal domain that is developmentally regulated. In nonerythroid cells, these genes replicate late in S phase, while in erythroid cells, replication is early. The replication origin is packaged with acetylated histones in erythroid cells, yet is associated with deacetylated histones in nonerythroid cells. Recruitment of histone acetylases to this origin brings about a transcription-independent shift to early replication in lymphocytes. In contrast, tethering of a histone deacetylase in erythroblasts causes a shift to late replication. These results suggest that histone modification at the origin serves as a binary switch for controlling replication timing.
Goren
Alon
A
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
Tabib
Amalia
A
Hecht
Merav
M
Cedar
Howard
H
D000107:Acetylation; D000818:Animals; D042522:DNA Replication Timing; D005914:Globins / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D018741:Replication Origin
D006657:Histones; D005914:Globins; D051548:Histone Acetyltransferases