CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing

Vo, Tommy V.; Dhakshnamoorthy, Jothy; Larkin, Madeline; Zofall, Martin; Thillainadesan, Gobi; Balachandran, Vanivilasini; Holla, Sahana; Wheeler, David; Grewal, Shiv I. S.

doi:10.1016/j.celrep.2019.05.107

Cited by 41 publications

(67 citation statements)

References 86 publications

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“…S5). This process parallels with the cleavage and polyadenylation factor (CPF)-mediated facultative heterochromatin assembly in yeast (33), the exact mechanism of which is still unknown.…”

Section: Discussionmentioning

confidence: 97%

The 3′ processing of antisense RNAs physically links to chromatin-based transcriptional control

Fang

Raitskin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Noncoding RNA plays essential roles in transcriptional control and chromatin silencing. AtArabidopsis thaliana FLC,antisense transcription quantitatively influences transcriptional output, but the mechanism by which this occurs is still unclear. Proximal polyadenylation of the antisense transcripts by FCA, an RNA-binding protein that physically interacts with RNA 3′ processing factors, reducesFLCtranscription. This process genetically requires FLD, a homolog of the H3K4 demethylase LSD1. However, the mechanism linking RNA processing to FLD function had not been established. Here, we show that FLD tightly associates with LUMINIDEPENDENS (LD) and SET DOMAIN GROUP 26 (SDG26) in vivo, and, together, they prevent accumulation of monomethylated H3K4 (H3K4me1) over theFLCgene body. SDG26 interacts with the RNA 3′ processing factor FY (WDR33), thus linking activities for proximal polyadenylation of the antisense transcripts to FLD/LD/SDG26-associated H3K4 demethylation. We propose this demethylation antagonizes an active transcription module, thus reducing H3K36me3 accumulation and increasing H3K27me3. Consistent with this view, we show that Polycomb Repressive Complex 2 (PRC2) silencing is genetically required by FCA to repressFLC. Overall, our work provides insights into RNA-mediated chromatin silencing.

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“…S5). This process parallels with the cleavage and polyadenylation factor (CPF)-mediated facultative heterochromatin assembly in yeast (33), the exact mechanism of which is still unknown.…”

Section: Discussionmentioning

confidence: 97%

The 3′ processing of antisense RNAs physically links to chromatin-based transcriptional control

Fang

Raitskin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…TRAMP containing Cid14, a member of the Trf4 family of poly(A) polymerases, targets RNAs into degradation machineries that include the exosome. Both RNAi-dependent and RNAi-independent mechanisms work in parallel to target CLRC to the repetitive DNA sequences located in the constitutive heterochromatin domains [71][72][73][74][75][76][77].…”

Section: Rnai-mediated Silencing Machinerymentioning

confidence: 99%

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Hirano

Asakawa

Sakuno

et al. 2020

Cells

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The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.

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Section: Parallel Examples Of Cotranscriptional Processing Linked Witmentioning

confidence: 99%

“…Related to Seb1, a recent study identified components of the cleavage and polyadenylation factor (CPF) complex as positive regulators of RNAi-independent heterochromatin silencing (Vo et al, 2019). A YTH family RNA-binding protein Mmi1 recruits CPF to the noncanonical termination sites, promoting termination of these noncoding genes and facilitating heterochromatin assembly (Vo et al, 2019). Notably, interaction between CPF and Seb1 was observed (Lemay et al, 2016;Wittmann et al, 2017;Larochelle et al, 2018), providing additional evidence that termination-related factors play important roles in gene silencing.…”

Section: Parallel Examples Of Cotranscriptional Processing Linked Witmentioning

confidence: 99%

Autonomous Pathway: FLOWERING LOCUS C Repression through an Antisense-Mediated Chromatin-Silencing Mechanism

et al. 2019

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The timing of flowering is vital for plant reproductive success and is therefore tightly regulated by endogenous and exogenous cues. In summer annual Arabidopsis (Arabidopsis thaliana) accessions, like Columbia-0, rapid flowering is promoted by repression of the floral repressor FLOWERING LOCUS C (FLC). This is through the activity of the autonomous pathway, a group of proteins with diverse functions including RNA 39-end processing factors, spliceosome components, a transcription elongation factor, and chromatin modifiers. These factors function at the FLC locus linking alternative processing of an antisense long noncoding RNA, called COOLAIR, with delivery of a repressive chromatin environment that affects the transcriptional output. The transcriptional output feeds back to influence the chromatin environment, reinforcing and stabilizing that state. This review summarizes our current knowledge of the autonomous pathway and compares it with similar cotranscriptional mechanisms in other organisms.

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CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing

Cited by 41 publications

References 86 publications

The 3′ processing of antisense RNAs physically links to chromatin-based transcriptional control

The 3′ processing of antisense RNAs physically links to chromatin-based transcriptional control

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Autonomous Pathway: FLOWERING LOCUS C Repression through an Antisense-Mediated Chromatin-Silencing Mechanism

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