Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain.
Female mammalian cells inactivate transcription from one of their X chromosomes to equalize gene expression of X-linked genes between males and females. Inactivation is a multistep process that involves a large non-coding RNA termed XIST, a variety of epigenetic modifications of chromatin, and alterations in protein composition such as enrichment of the histone variant macroH2A. We show here that inactive X chromosomes are also enriched in a well-characterized protein component of the nuclear scaffold, SAF-A. This protein has been implicated in chromatin organization, owing to its high specificity for scaffold-associated region (SAR)-DNA, in transcriptional regulation, e.g. of hormone-regulated genes, owing to its functional interaction with steroid receptors, and in RNA processing, owing to its interaction with RNA and heterogeneous nuclear ribonucleoprotein (hnRNP) particles. After near complete removal of DNA and associated chromatin proteins such as macroH2A, SAF-A remains with the "nuclear matrix", still highlighting the former position of inactive X chromosomes. Interestingly, the enrichment of SAF-A in the inactive X chromosome depends on the RNA binding domain of the protein, the RGG box, raising the possibility that interaction of SAF-A with XIST RNA may contribute to the silencing of X-linked genes by local changes in nuclear architecture.
Helbig
Roger
R
Department of Molecular Cell Biology, Heinrich-Pette-Institute, Martinistrasse 52, 20251 Hamburg, Germany.
Fackelmayer
Frank O
FO
D002478:Cells, Cultured; D041321:Chromosomes, Human, X / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D004303:Dosage Compensation, Genetic; D005455:Fluorescent Antibody Technique; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000378:metabolism*; D006801:Humans; D015530:Nuclear Matrix / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*
D017931:DNA Primers; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA