X chromosome imprinting and inactivation in the early mammalian embryo.
Quantitative differences in X-linked gene expression between androgenetic (two paternal genomes), gynogenetic (two maternal genomes) and normal embryos provide clues into the roles of genomic imprinting and the X:autosome ratio in controlling X chromosome function during development. These data and many others can be accounted for by a new model of X-chromosome-inactivation (XCI). Expression of the Xist RNA from all paternal X chromosomes during development preimplantation leads to repression of genes near the X-chromosome-inactivation center (Xic). Other genes are repressed as a result of spreading of the inactivation, but only in embryos with at least two X chromosomes. XY androgenones are only deficient in expression of genes near the Xic and can form blastocysts, whereas XX androgenones completely inactivate both X chromosomes and die before the blastocyst stage. The X:autosome ratio regulates XCI solely by promoting the spread of inactivation away from the Xic on chromosomes that express Xist. Methylation of the maternal Xist gene is retained in extraembryonic tissues, so that gynogenones and parthenogenones cannot express Xist, do not undergo XCI in those tissues, and so have extraembryonic defects. This model should be relevant to understanding how aberrant X chromosome regulation might occur and how this might contribute to distortion of the X-chromosome-transmission ratio, sex ratio distortion, and disease.
Latham
K E
KE
Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA. keith@cleo.fels.temple.edu
D000818:Animals; D001755:Blastocyst; D004303:Dosage Compensation, Genetic; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D008297:Male; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors / Q000502:physiology; D014960:X Chromosome
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA