The matrix protein hnRNP U is required for chromosomal localization of Xist RNA.
In XX female mammals, one of the two X chromosomes is epigenetically inactivated to equalize gene expression with XY males. The formation of the inactive X chromosome (Xi) is regulated by an X-linked long noncoding RNA Xist, which accumulates on the entire length of the chromosome in cis and induces heterochromatin formation. However, the mechanism by which Xist RNA "paints" the Xi has long remained elusive. Here, we show that a matrix protein hnRNP U/SP120/SAF-A is required for the accumulation of Xist RNA on the Xi. Xist RNA and hnRNP U interact and upon depletion of hnRNP U, Xist RNA is detached from the Xi and diffusely localized into the nucleoplasm. In addition, ES cells lacking hnRNP U expression fail to form the Xi. We propose that the association with matrix proteins is an essential step in the epigenetic regulation of gene expression by Xist RNA.
Hasegawa
Yuko
Y
RNA Biology Laboratory, RIKEN Advanced Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Brockdorff
Neil
N
Kawano
Shinji
S
Tsutui
Kimiko
K
Tsutui
Ken
K
Nakagawa
Shinichi
S
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006570:Heterochromatin / Q000235:genetics; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049951:X Chromosome Inactivation
D006570:Heterochromatin; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D006657:Histones; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; C077885:XIST non-coding RNA