Ageing-related chromatin defects through loss of the NURD complex.
Physiological and premature ageing are characterized by multiple defects in chromatin structure and accumulation of persistent DNA damage. Here we identify the NURD chromatin remodelling complex as a key modulator of these ageing-associated chromatin defects. We demonstrate loss of several NURD components during premature and normal ageing and we find an ageing-associated reduction in HDAC1 activity. Silencing of individual NURD subunits recapitulated chromatin defects associated with ageing and we provide evidence that structural chromatin defects precede DNA damage accumulation. These results outline a molecular mechanism for chromatin defects during ageing.
Pegoraro
Gianluca
G
National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Kubben
Nard
N
Wickert
Ute
U
Göhler
Heike
H
Hoffmann
Katrin
K
Misteli
Tom
T
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002648:Child; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D019175:DNA Methylation; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002843:Chromatin; D021122:Protein Subunits; D034741:RNA, Small Interfering; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex