A conserved, extended chromatin opening within alpha-globin locus during development.
Histone modifications play an important role in eukaryotic gene regulation. However, the dynamic alteration of histone modification during development is poorly understood. In addition, the relationship between histone modification and globin gene switching remains unclear. Here, we assessed the dynamic pattern of histone modification (H3 acetylation, H4 acetylation, H3 K4 methylation, and H3 K79 methylation) along the murine alpha-globin locus, as well as along the human alpha-globin locus in transgenic mice, during globin gene switching in vivo. During the switching, histone modification at embryonic zeta-gene and fetal/adult alpha-genes displayed different developmental patterns. The level of histone modification at zeta-gene was developmentally regulated, in accordance with the level of zeta-gene expression, whereas the alpha-genes kept high level of histone modification at both developmental stages, regardless of their expression levels. Histone deacetylase inhibition selectively increased acetylation at the inactive zeta-gene in fetal livers, although it did not reactivate the gene expression. More importantly, an obvious increasing of histone modification level at major regulatory elements and fetal/adult alpha-genes was observed during the switching, suggesting that a conserved, extended chromatin opening within the locus occurs during globin gene switching.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, P.R. China.
Xiang-Hui
XH
Fu
De-Pei
DP
Liu
Xiao-Bin
XB
Tang
Guang
G
Liu
Xiang
X
Lv
Ya-Jun
YJ
Li
Chih-Chuan
CC
Liang
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005812:Genes, Switch; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic
D002843:Chromatin; D006657:Histones; D005914:Globins; D006655:Histone Deacetylases