Identification of TSIX, Encoding an RNA Antisense to Human XIST, Reveals Differences from its Murine Counterpart: Implications for X Inactivation

• Published in: American journal of human genetics Vol. 69; no. 5; pp. 951 - 960
• Main Authors: Migeon, Barbara R., Chowdhury, Ashis K., Dunston, Jennifer A., McIntosh, Iain
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.11.2001; University of Chicago Press; The American Society of Human Genetics
• Subjects: Aging - genetics; Animals; Biological and medical sciences; Cell Line; Dosage Compensation, Genetic; Embryo, Mammalian - metabolism; Evolution, Molecular; Fetus - metabolism; General aspects. Genetic counseling; Genomic Imprinting - genetics; Humans; Medical genetics; Medical sciences; Mice; Molecular Sequence Data; Open Reading Frames - genetics; Placenta - metabolism; RNA, Antisense - analysis; RNA, Antisense - biosynthesis; RNA, Antisense - genetics; RNA, Antisense - isolation & purification; RNA, Long Noncoding; RNA, Untranslated - analysis; RNA, Untranslated - biosynthesis; RNA, Untranslated - genetics; RNA, Untranslated - isolation & purification; Sequence Deletion - genetics; Sequence Homology, Nucleic Acid; Species Specificity; Stem Cells - metabolism; Transcription Factors - genetics; Transcription Initiation Site; Transcription, Genetic; Transgenes - genetics; TSIX gene; XIST gene; Human; Embryonic development; Embryo; Sex chromosome; Rodentia; Exploration; Antisense RNA; Gene expression; Inactivation; Genetic determinism; Genomic imprinting; Vertebrata; Mammalia; Placenta; Gene; Mouse; Animal; X-Chromosome; Comparative study
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/324022

X inactivation is the mammalian method for X-chromosome dosage compensation, but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pathway. Tsix encodes a transcript antisense to the murine Xist transcript and is expressed in the mouse embryo only during the initial stages of X inactivation; it has been shown to play a role in imprinted X inactivation in the mouse placenta. We have identified its counterpart within the human X inactivation center ( XIC). Human TSIX produces a >30-kb transcript that is expressed only in cells of fetal origin; it is expressed from human XIC transgenes in mouse embryonic stem cells and from human embryoid-body–derived cells, but not from human adult somatic cells. Differences in the structure of human and murine genes indicate that human TSIX was truncated during evolution. These differences could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSIX in random X inactivation.