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Nucleic Acids Res. 2013 May 1;41(10):5251-62. doi: 10.1093/nar/gkt218. Epub 2013 Apr 10.

Large-scale organization of ribosomal DNA chromatin is regulated by Tip5.

Author information

  • 1Department of Biochemistry III, Biochemistry Center Regensburg, University of Regensburg, Universitätsstr 31, D-93053 Regensburg, Germany.

Abstract

The DNase I accessibility and chromatin organization of genes within the nucleus do correlate to their transcriptional activity. Here, we show that both serum starvation and overexpression of Tip5, a key regulator of ribosomal RNA gene (rDNA) repression, dictate DNase I accessibility, facilitate the association of rDNA with the nuclear matrix and thus regulate large-scale rDNA chromatin organization. Tip5 contains four AT-hooks and a TAM (Tip5/ARBP/MBD) domain, which were proposed to bind matrix-attachment regions (MARs) of the genome. Remarkably, the TAM domain of Tip5 functions as nucleolar localization and nuclear matrix targeting module, whereas AT-hooks do not mediate association with the nuclear matrix, but they are required for nucleolar targeting. These findings suggest a dual role for Tip5's AT-hooks and TAM domain, targeting the nucleolus and anchoring to the nuclear matrix, and suggest a function for Tip5 in the regulation of higher-order rDNA chromatin structure.

PMID:
23580549
[PubMed - indexed for MEDLINE]
PMCID:
PMC3664807
Free PMC Article

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