Mechanisms that establish and propagate the epigenetic state of rRNA genes.

Ribosomal genes (rDNA) exist in two distinct types of chromatin, an 'open’ one that is permissive to transcription and a 'closed’ one that is transcriptionally refractive. The mechanisms that maintain the ratio of active vs. silent rDNA repeats are poorly understood, but silencing is one of the factors that influences transcriptional activity. Switching between the active and silent state is mediated by a chromatin remodelling complex, called NoRC, that binds to the rDNA promoter, shifts nucleosomes into an ‚inactive’ position and establishes heterochromatic features by recruiting DNA- and histone-modifying enzymes, thus leading to transcriptional silencing. Importantly, NoRC function requires binding to ‘pRNA’, 150-250 nt RNAs that are complementary in sequence to the rDNA promoter (Mayer et al. 2006; 2008). We are investigating the role of ‘pRNA’ in sense and antisense orientation in epigenetic regulation, the contribution of posttranslational modifications in NoRC function and the mechanism that links the epigenetic state of rDNA to cell metabolism. In the long term, these studies will lead to an understanding of the mechanisms that propagate the active and silent state of rRNA genes through cell division and will reveal how epigenetic defects cause human diseases.
Domain: Molekularbiologie


K.M. Schmitz, N. Schmitt, U. Hoffmann-Rohrer, A. Schäfer, I. Grummt, C. Mayer. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of active genes leading to DNA demethylation. Molecular Cell (Februar 2009).

B. McStay, B. and I. Grummt. The epigenetics of rRNA genes, from molecular to chromosome biology. Ann. Rev, Cell Dev, Biol. (Juli 2008)

I. Grummt and A.G. Ladurner. A metabolic throttle regulates the epigenetic state of rDNA. Cell (Mai 2008)



Prof. Dr. Ingrid Grummt
Deutsches Krebsforschungszentrum
Molekularbiologie der Zelle II
Im Neuenheimer Feld 581
69120 Heidelberg, Germany

Phone: +49 6221 423423
Fax: +49 6221 423467