High-affinity binding of Chp1 chromodomain to K9 methylated histone H3 is required to establish centromeric heterochromatin.
In fission yeast, assembly of centromeric heterochromatin requires the RITS complex, which consists of Ago1, Tas3, Chp1, and siRNAs derived from centromeric repeats. Recruitment of RITS to centromeres has been proposed to depend on siRNA-dependent targeting of Ago1 to centromeric sequences. Previously, we demonstrated that methylated lysine 9 of histone H3 (H3K9me) acts upstream of siRNAs during heterochromatin establishment. Our crystal structure of Chp1's chromodomain in complex with a trimethylated lysine 9 H3 peptide reveals extensive sites of contact that contribute to Chp1's high-affinity binding. We found that this high-affinity binding is critical for the efficient establishment of centromeric heterochromatin, but preassembled heterochromatin can be maintained when Chp1's affinity for H3K9me is greatly reduced.
Schalch
Thomas
T
Keck Structural Biology Laboratory, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Job
Godwin
G
Noffsinger
Victoria J
VJ
Shanker
Sreenath
S
Kuscu
Canan
C
Joshua-Tor
Leemor
L
Partridge
Janet F
JF
D000595:Amino Acid Sequence; D060565:Argonaute Proteins; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D018360:Crystallography, X-Ray; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
C481643:Ago1 protein, S pombe; D060565:Argonaute Proteins; D018797:Cell Cycle Proteins; C115018:Chp1 protein, S pombe; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D008239:Lysine