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J Mol Cell Biol. 2012 Aug;4(4):231-41. doi: 10.1093/jmcb/mjs003. Epub 2012 Feb 24.

Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.

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Department of Biochemistry and Molecular Biology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.


Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the occupancy of not only the Brg1 complex but also the Pol I complex at the core promoter and enhances transcription initiation of rRNA genes. Additionally, the interaction between PIH1 and H4K16 expels TIP5, a component of the silencing nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1 is involved in the derepression of NoRC-silenced rRNA genes. These data indicate that PIH1 is a positive regulator of human rRNA genes and is of great importance for the recovery of human cells from nutrient starvation and the transition to glucose-induced exponential growth in vivo.

[Indexed for MEDLINE]

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