SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle

TY - JOUR

T1 - SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle

AU - Iyer-Bierhoff, Aishwarya

AU - Krogh, Nicolai

AU - Tessarz, Peter

AU - Ruppert, Thomas

AU - Nielsen, Henrik

AU - Grummt, Ingrid

PY - 2018/12/11

Y1 - 2018/12/11

N2 - Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2′-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. While reversible acetylation does not impact FBL-mediated pre-rRNA methylation, hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. At the onset of mitosis, nucleolar disassembly is accompanied by hyperacetylation of FBL, loss of H2AQ104me, and repression of polymerase I (Pol I) transcription. Overexpression of an acetylation-deficient, but not an acetylation-mimicking, FBL mutant restores H2AQ104me and transcriptional activity. The results reveal that SIRT7-dependent deacetylation impacts nucleolar activity by an FBL-driven circuitry that mediates cell-cycle-dependent fluctuation of rDNA transcription. Iyer-Bierhoff et al. show that reversible acetylation of fibrillarin (FBL) regulates methylation of histone H2A at glutamine 104 (H2AQ104) and controls rDNA transcription. The study identifies a mechanism underlying cell-cycle-dependent fluctuations in H2AQ104 methylation and rRNA synthesis driven by SIRT7-mediated deacetylation of FBL.

AB - Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2′-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. While reversible acetylation does not impact FBL-mediated pre-rRNA methylation, hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. At the onset of mitosis, nucleolar disassembly is accompanied by hyperacetylation of FBL, loss of H2AQ104me, and repression of polymerase I (Pol I) transcription. Overexpression of an acetylation-deficient, but not an acetylation-mimicking, FBL mutant restores H2AQ104me and transcriptional activity. The results reveal that SIRT7-dependent deacetylation impacts nucleolar activity by an FBL-driven circuitry that mediates cell-cycle-dependent fluctuation of rDNA transcription. Iyer-Bierhoff et al. show that reversible acetylation of fibrillarin (FBL) regulates methylation of histone H2A at glutamine 104 (H2AQ104) and controls rDNA transcription. The study identifies a mechanism underlying cell-cycle-dependent fluctuations in H2AQ104 methylation and rRNA synthesis driven by SIRT7-mediated deacetylation of FBL.

KW - acetylation

KW - cell cycle

KW - chromatin

KW - fibrillarin

KW - glutamine methylation

KW - histone H2A

KW - nucleolus

KW - rRNA

KW - SIRT7

KW - transcription

U2 - 10.1016/j.celrep.2018.11.051

DO - 10.1016/j.celrep.2018.11.051

M3 - Journal article

C2 - 30540930

AN - SCOPUS:85057412924

SN - 2639-1856

VL - 25

SP - 2946

EP - 2954

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -