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Reference - PMID:38048463 - Rex1BD and the 14-3-3 protein control heterochromatin organization at tandem repeats by linking RNAi and HDAC.

Reference summary

PubMed ID
PMID:38048463
Title
Rex1BD and the 14-3-3 protein control heterochromatin organization at tandem repeats by linking RNAi and HDAC.
Authors
Gao J, Sun W, Li J, Ban H, Zhang T, Liao J, Kim N, Lee SH, Dong Q, Madramootoo R, Chen Y, Li F
Citation
Proc Natl Acad Sci U S A 2023 Dec 12;120(50):e2309359120
Publication year
2023
Abstract
Tandem DNA repeats are often organized into heterochromatin that is crucial for genome organization and stability. Recent studies revealed that individual repeats within tandem DNA repeats can behave very differently. How DNA repeats are assembled into distinct heterochromatin structures remains poorly understood. Here, we developed a genome-wide genetic screen using a reporter gene at different units in a repeat array. This screen led to identification of a conserved protein Rex1BD required for heterochromatin silencing. Our structural analysis revealed that Rex1BD forms a four-helix bundle structure with a distinct charged electrostatic surface. Mechanistically, Rex1BD facilitates the recruitment of Clr6 histone deacetylase (HDAC) by interacting with histones. Interestingly, Rex1BD also interacts with the 14-3-3 protein Rad25, which is responsible for recruiting the RITS (RNA-induced transcriptional silencing) complex to DNA repeats. Our results suggest that coordinated action of Rex1BD and Rad25 mediates formation of distinct heterochromatin structure at DNA repeats via linking RNAi and HDAC pathways.

Annotation

GO biological process

GO:0031508 - pericentric heterochromatin formation

Genes:

GO:0031509 - subtelomeric heterochromatin formation

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GO:0140727 - siRNA-mediated pericentric heterochromatin formation

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GO cellular component

GO:0005634 - nucleus

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Multi-locus phenotype

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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Genotypes:

FYPO:0003010 - increased protein localization to subtelomeric heterochromatin during vegetative growth

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Genotypes:

Single locus phenotype

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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FYPO:0002827 - decreased chromatin silencing at silent mating-type cassette

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FYPO:0004604 - decreased chromatin silencing at subtelomere

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Genotypes:

FYPO:0000888 - decreased histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0002386 - decreased protein localization to pericentric heterochromatin at centromere outer repeat region

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FYPO:0002387 - decreased protein localization to subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0006814 - increased histone H3-K9 acetylation at centromere outer repeat during vegetative growth

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FYPO:0002336 - normal chromatin silencing at silent mating-type cassette

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FYPO:0003555 - normal chromatin silencing at subtelomere

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Genotypes:

FYPO:0003576 - normal protein localization to subtelomeric heterochromatin

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Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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