title: Repressive but not activating epigenetic modifications are aberrant on the inactive X chromosome in live cloned cattle.
abstract: X inactivation is the process of a chromosome-wide silencing of the majority of genes on the X chromosome during early mammalian development. This process may be aberrant in cloned animals. Here we show that repressive modifications, such as methylation of DNA, and the presence of methylated histones, H3K9me2 and H3K27me3, exhibit distinct aberrance on the inactive X chromosome in live clones. In contrast, H3K4me3, an active gene marker, is obviously missing from the inactive X chromosome in all cattle studied. This suggests that the disappearance of active histone modifications (H3K4me3) seems to be more important for X inactivation than deposition of marks associated with heterochromatin (DNA methylation, H3K27me3 and H3K9me2). It also implies that even apparently normal clones may have subtle abnormalities in repressive, but not activating epigenetic modifications on the inactive X when they survive to term. We also found that the histone H3 methylations were enriched and co-localized at q21-31 of the active X chromosome, which may be associated with an abundance of LINE1 repeat elements.
authors.affiliation: Department of Biochemistry and Molecular Biology, China Agricultural University, Beijing 100193, China. gengsheng_cao@hotmail.com
authors.forename: Cao
authors.initials: C
authors.lastname: Geng-Sheng
authors.forename: Gao
authors.initials: G
authors.lastname: Yu
authors.forename: Wang
authors.initials: W
authors.lastname: Kun
authors.forename: Ding
authors.initials: D
authors.lastname: Fang-Rong
authors.forename: Li
authors.initials: L
authors.lastname: Ning
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D019976:Cloning, Organism; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000032:analysis; D004303:Dosage Compensation, Genetic; D044127:Epigenesis, Genetic; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D020084:Long Interspersed Nucleotide Elements; D008745:Methylation; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D015226:Dinucleoside Phosphates; D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; C015772:CpG dinucleotide