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X‐chromosome inactivation: Sex, heterochromatin, pairing, and noncoding RNA
Author(s) -
Lee Jeannie T.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.396.2
Subject(s) - xist , x inactivation , x chromosome , biology , genetics , heterochromatin , dosage compensation , germline , rna , pairing , skewed x inactivation , chromosome , gene , physics , superconductivity , quantum mechanics
X‐chromosome inactivation (XCI) ensures that XY male and XX female mammals have equal X‐chromosome dosage. XCI takes place in both males and females. In females, one of two Xs is inactivated in the virtually all tissues of the soma. In males, both X and Y chromosomes become inactivated in the germline. One aspect of XCI that has particularly interested us is the fact that the somatic form depends on an X‐linked region (the ‘X‐inactivation center’) known for its abundance of long non‐coding transcripts. Working together, the three non‐coding elements, Xite, Tsix, and Xist, control the initiation of silencing along the entire X‐chromosome, resulting in the ‘coating’ of one X‐chromosome by Xist RNA and the recruitment of heterochromatic factors to that X in cis. While many steps of XCI are regulated in a cis‐limited fashion, XCI must in principle also be regulated in trans. Our recent work suggests that the two Xs communicate with each other in trans to ensure that the choice of active and inactive Xs occur in a mutually exclusive fashion. This trans‐communication apparently involves transient homologous pairing of the two Xs just prior to XCI. Pairing is absolutely essential and requires the non‐coding elements, Tsix and Xite. I will discuss our latest discoveries on the molecular aspects of these regulatory processes.