SUV39 SET domains mediate crosstalk of heterochromatic histone marks

Research output: Contribution to journal › Journal article › Research › peer-review

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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

Harvard

Stirpe, A, Guidotti, N, Northall, SJ, Kilic, S, Hainard, A, Vadas, O, Fierz, B & Schalch, T 2021, 'SUV39 SET domains mediate crosstalk of heterochromatic histone marks', eLife, vol. 10, 62682. https://doi.org/10.7554/eLife.62682

APA

Stirpe, A., Guidotti, N., Northall, S. J., Kilic, S., Hainard, A., Vadas, O., Fierz, B., & Schalch, T. (2021). SUV39 SET domains mediate crosstalk of heterochromatic histone marks. eLife, 10, [62682]. https://doi.org/10.7554/eLife.62682

Vancouver

Stirpe A, Guidotti N, Northall SJ, Kilic S, Hainard A, Vadas O et al. SUV39 SET domains mediate crosstalk of heterochromatic histone marks. eLife. 2021;10. 62682. https://doi.org/10.7554/eLife.62682

Author

Stirpe, Alessandro ; Guidotti, Nora ; Northall, Sarah J. ; Kilic, Sinan ; Hainard, Alexandre ; Vadas, Oscar ; Fierz, Beat ; Schalch, Thomas. / SUV39 SET domains mediate crosstalk of heterochromatic histone marks. In: eLife. 2021 ; Vol. 10.

Bibtex

@article{07aafa5ec1214c98b80213dabee83c1c,
title = "SUV39 SET domains mediate crosstalk of heterochromatic histone marks",
abstract = "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.",
keywords = "FISSION YEAST, UBIQUITIN LIGASE, HP1 PROTEINS, RNAI, METHYLTRANSFERASE, CLR4, ROLES, METHYLATION, NUCLEATION, COMPLEX",
author = "Alessandro Stirpe and Nora Guidotti and Northall, {Sarah J.} and Sinan Kilic and Alexandre Hainard and Oscar Vadas and Beat Fierz and Thomas Schalch",
year = "2021",
doi = "10.7554/eLife.62682",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

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