Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development.
Escape from X inactivation results in expression of genes embedded within inactive chromatin, suggesting the existence of boundary elements between domains. We report that the 5' end of Jarid1c, a mouse escape gene adjacent to an inactivated gene, binds CTCF, displays high levels of histone H3 acetylation, and functions as a CTCF-dependent chromatin insulator. CpG island methylation at Jarid1c was very low during development and virtually absent at the CTCF sites, signifying that CTCF may influence DNA methylation and chromatin modifications. CTCF binding sites were also present at the 5' end of two other escape genes, mouse Eif2s3x and human EIF2S3, each adjacent to an inactivated gene, but not at genes embedded within large escape domains. Thus, CTCF was specifically bound to transition regions, suggesting a role in maintaining both X inactivation and escape domains. Furthermore, the evolution of X chromosome domains appears to be associated with repositioning of chromatin boundary elements.
Filippova
Galina N
GN
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. gfilippo@fhcrc.org
Cheng
Mimi K
MK
Moore
James M
JM
Truong
Jean-Pierre
JP
Hu
Ying J
YJ
Nguyen
Di Kim
DK
Tsuchiya
Karen D
KD
Disteche
Christine M
CM
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D056466:Histone Demethylases; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010089:Oxidoreductases, N-Demethylating; D011506:Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014960:X Chromosome
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D011506:Proteins; D012097:Repressor Proteins; D056466:Histone Demethylases; C490173:Kdm5c protein, mouse; D010089:Oxidoreductases, N-Demethylating