Structural dynamics and epigenetic modifications of Hoxc loci along the anteroposterior body axis in developing mouse embryos.
Hox genes are organized as clusters and specify regional identity along the anteroposterior body axis by sequential expression at a specific time and region during embryogenesis. However, the precise mechanisms underlying the sequential spatio-temporal, collinear expression pattern of Hox genes are not fully understood. Since epigenetic modifications such as chromatin architecture and histone modifications have become crucial mechanisms for highly coordinated gene expressions, we examined such modifications. E14.5 mouse embryos were dissected into three parts along the anteroposterior axis: brain, trunk-anterior, and trunk-posterior. Then, structural changes and epigenetic modifications were analyzed along the Hoxc cluster using chromosome conformation capture and chromatin immunoprecipitation-PCR methods. Hox non-expressing brain tissues had more compact, heterochromatin-like structures together with the strong repressive mark H3K27me3 than trunk tissues. In the trunk, however, a more loose euchromatin-like topology with a reduced amount of H3K27me3 modifications were observed along the whole cluster, regardless of their potency in gene activation. The active mark H3K4me3 was rather closely associated with the collinear expression of Hoxc genes; at trunk-anterior tissues, only 3' anterior Hoxc genes were marked by H3K4me3 upon gene activation, whereas whole Hoxc genes were marked by H3K4me3 and showed expression in trunk-posterior tissues. Altogether, these results indicated that loosening of the chromatin architecture and removing H3K27me3 were not sufficient for, but rather the concomitant acquisition of H3K4me3 drove the collinear expression of Hoxc genes.
Department of Anatomy, Embryology Laboratory, Brain Korea 21 project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea. mhkim1@yuhs.ac
Hyehyun
H
Min
Ji-Yeon
JY
Lee
Myoung Hee
MH
Kim
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D002843:Chromatin; D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse; C065404:Hoxc9 protein, mouse; C084118:Hoxd13 protein, mouse; D014157:Transcription Factors