SUV39 SET domains mediate crosstalk of heterochromatic histone marks
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SUV39 SET domains mediate crosstalk of heterochromatic histone marks. / Stirpe, Alessandro; Guidotti, Nora; Northall, Sarah J.; Kilic, Sinan; Hainard, Alexandre; Vadas, Oscar; Fierz, Beat; Schalch, Thomas.
In: eLife, Vol. 10, 62682, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - SUV39 SET domains mediate crosstalk of heterochromatic histone marks
AU - Stirpe, Alessandro
AU - Guidotti, Nora
AU - Northall, Sarah J.
AU - Kilic, Sinan
AU - Hainard, Alexandre
AU - Vadas, Oscar
AU - Fierz, Beat
AU - Schalch, Thomas
PY - 2021
Y1 - 2021
N2 - Y The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.
AB - Y The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poorly understood. Clr4 is the sole H3K9me2/3 methyltransferase in the fission yeast Schizosaccharomyces pombe, and recent evidence suggests that ubiquitination of lysine 14 on histone H3 (H3K14ub) plays a key role in H3K9 methylation. However, the molecular mechanism of this regulation and its role in heterochromatin formation remain to be determined. Our structure-function approach shows that the H3K14ub substrate binds specifically and tightly to the catalytic domain of Clr4, and thereby stimulates the enzyme by over 250-fold. Mutations that disrupt this mechanism lead to a loss of H3K9me2/3 and abolish heterochromatin silencing similar to clr4 deletion. Comparison with mammalian SET domain proteins suggests that the Clr4 SET domain harbors a conserved sensor for H3K14ub, which mediates licensing of heterochromatin formation.
KW - FISSION YEAST
KW - UBIQUITIN LIGASE
KW - HP1 PROTEINS
KW - RNAI
KW - METHYLTRANSFERASE
KW - CLR4
KW - ROLES
KW - METHYLATION
KW - NUCLEATION
KW - COMPLEX
U2 - 10.7554/eLife.62682
DO - 10.7554/eLife.62682
M3 - Journal article
C2 - 34524082
VL - 10
JO - eLife
JF - eLife
SN - 2050-084X
M1 - 62682
ER -
ID: 280234365