Journal
GENES & DEVELOPMENT
Volume 22, Issue 10, Pages 1319-1324Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.468308
Keywords
replication timing; chromatin structure; epigenetics; gene expression; development
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The human beta-globin genes constitute a large chromosomal domain that is developmentally regulated. In non-erythroid 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.
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