Epigenetic regulation of condensin-mediated genome organization during the cell cycle and upon DNA damage through histone H3 lysine 56 acetylation.
Complex genome organizations participate in various nuclear processes including transcription, DNA replication, and repair. However, the mechanisms that generate and regulate these functional genome structures remain largely unknown. Here, we describe how the Ku heterodimer complex, which functions in nonhomologous end joining, mediates clustering of long terminal repeat retrotransposons at centromeres in fission yeast. We demonstrate that the CENP-B subunit, Abp1, functions as a recruiter of the Ku complex, which in turn loads the genome-organizing machinery condensin to retrotransposons. Intriguingly, histone H3 lysine 56 (H3K56) acetylation, which functions in DNA replication and repair, interferes with Ku localization at retrotransposons without disrupting Abp1 localization and, as a consequence, dissociates condensin from retrotransposons. This dissociation releases condensin-mediated genomic associations during S phase and upon DNA damage. ATR (ATM- and Rad3-related) kinase mediates the DNA damage response of condensin-mediated genome organization. Our study describes a function of H3K56 acetylation that neutralizes condensin-mediated genome organization.
Department of Gene Expression and Regulation, The Wistar Institute, Philadelphia, PA 19104, USA.
Atsunari
A
Tanaka
Hideki
H
Tanizawa
Sira
S
Sriswasdi
Osamu
O
Iwasaki
Atreyi G
AG
Chatterjee
David W
DW
Speicher
Henry L
HL
Levin
Eishi
E
Noguchi
Ken-Ichi
K
Noma
D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D004249:DNA Damage; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D016678:Genome; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
C062612:ABP1 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D006657:Histones; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases; D008239:Lysine