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PMID: 18443145 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

DNA replication timing of the human beta-globin domain is controlled by histone modification at the origin.

Genes & development ·Vol. 22 ·No. 10 ·2008-05-15 ·Pages 1319-24

Goren A, Tabib A, Hecht M, Cedar H

Abstract

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.

MeSH Terms
Acetylation Animals DNA Replication Timing Globins/genetics Histone Acetyltransferases/metabolism Histones/metabolism Humans Mice Mice, Transgenic Protein Processing, Post-Translational/physiology Protein Structure, Tertiary/genetics Replication Origin
Chemicals
Histones Globins Histone Acetyltransferases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Goren Alon
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
Tabib Amalia
Hecht Merav
Cedar Howard
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.468308
Published
2008-05-15
Epub
2008-00-28
Pages
1319-24
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2377185
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.468308 PMC Full Text View journal details
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