TY - JOUR
T1 - Dri1 mediates heterochromatin assembly via RNAi and histone deacetylation
AU - Ban, Hyoju
AU - Sun, Wenqi
AU - Chen, Yu Hang
AU - Chen, Yong
AU - Li, Fei
N1 - Funding Information:
This project was supported in part by National Institutes of Health grant R35GM134920-01 (to F.L.) and National Science Foundation grant MCB-1934628 (to F.L.).
Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Heterochromatin, a transcriptionally silenced chromatin domain, is important for genome stability and gene expression. Histone 3 lysine 9 methylation (H3K9me) and histone hypoacetylation are conserved epigenetic hallmarks of heterochromatin. In fission yeast, RNA interference (RNAi) plays a key role in H3K9 methylation and heterochromatin silencing. However, how RNAi machinery and histone deacetylases (HDACs) are coordinated to ensure proper heterochromatin assembly is still unclear. Previously, we showed that Dpb4, a conserved DNA polymerase epsilon subunit, plays a key role in the recruitment of HDACs to heterochromatin during S phase. Here, we identified a novel RNA-binding protein Dri1 that interacts with Dpb4. GFP-tagged Dri1 forms distinct foci mostly in the nucleus, showing a high degree of colocalization with Swi6/ Heterochromatin Protein 1. Deletion of dri1þ leads to defects in silencing, H3K9me, and heterochromatic siRNA generation. We also showed that Dri1 physically associates with heterochromatic transcripts, and is required for the recruitment of the RNA-induced transcriptional silencing (RITS) complex via interacting with the complex. Furthermore, loss of Dri1 decreases the association of the Sir2 HDAC with heterochromatin. We further demonstrated that the C-terminus of Dri1 that includes an intrinsically disordered (IDR) region and three zinc fingers is crucial for its role in silencing. Together, our evidences suggest that Dri1 facilitates heterochromatin assembly via the RNAi pathway and HDAC.
AB - Heterochromatin, a transcriptionally silenced chromatin domain, is important for genome stability and gene expression. Histone 3 lysine 9 methylation (H3K9me) and histone hypoacetylation are conserved epigenetic hallmarks of heterochromatin. In fission yeast, RNA interference (RNAi) plays a key role in H3K9 methylation and heterochromatin silencing. However, how RNAi machinery and histone deacetylases (HDACs) are coordinated to ensure proper heterochromatin assembly is still unclear. Previously, we showed that Dpb4, a conserved DNA polymerase epsilon subunit, plays a key role in the recruitment of HDACs to heterochromatin during S phase. Here, we identified a novel RNA-binding protein Dri1 that interacts with Dpb4. GFP-tagged Dri1 forms distinct foci mostly in the nucleus, showing a high degree of colocalization with Swi6/ Heterochromatin Protein 1. Deletion of dri1þ leads to defects in silencing, H3K9me, and heterochromatic siRNA generation. We also showed that Dri1 physically associates with heterochromatic transcripts, and is required for the recruitment of the RNA-induced transcriptional silencing (RITS) complex via interacting with the complex. Furthermore, loss of Dri1 decreases the association of the Sir2 HDAC with heterochromatin. We further demonstrated that the C-terminus of Dri1 that includes an intrinsically disordered (IDR) region and three zinc fingers is crucial for its role in silencing. Together, our evidences suggest that Dri1 facilitates heterochromatin assembly via the RNAi pathway and HDAC.
KW - HDAC
KW - RNAi pathway
KW - Schizosaccharomyces pombe
KW - heterochromatin
KW - Heterochromatin/genetics
KW - Cell Nucleus/metabolism
KW - Chromatin/metabolism
KW - DNA Polymerase II/metabolism
KW - RNA, Small Interfering/genetics
KW - Chromosomal Proteins, Non-Histone/genetics
KW - Chromatin Assembly and Disassembly/genetics
KW - RNA Interference
KW - Histone-Lysine N-Methyltransferase/metabolism
KW - Acetylation
KW - Histones/genetics
KW - Schizosaccharomyces pombe Proteins/genetics
KW - Methylation
KW - Schizosaccharomyces/genetics
UR - http://www.scopus.com/inward/record.url?scp=85107082312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107082312&partnerID=8YFLogxK
U2 - 10.1093/genetics/iyab032
DO - 10.1093/genetics/iyab032
M3 - Article
C2 - 33693625
AN - SCOPUS:85107082312
SN - 0016-6731
VL - 218
JO - Genetics
JF - Genetics
IS - 1
M1 - iyab032
ER -