Iron homeostasis regulates facultative heterochromatin assembly in adaptive genome control

Larkin, Madeline; Thillainadesan, Gobi; Dhakshnamoorthy, Jothy; Balachandran, Vanivilasini; Xiao, Hua; Wellman, Christopher Heath; Chatterjee, Raghunath; Wheeler, David; Grewal, Shiv I. S.

doi:10.1038/s41594-018-0056-2

Cited by 33 publications

(35 citation statements)

References 73 publications

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“…In addition, we examined islands of facultative heterochromatin that accumulate H3K9me2 in response to stress 30 and detected three islands enriched in H3K9me2 in spH2A.W At , but not in WT and spH2A.W4A At (Figures 4E and 4F). These heterochromatin islands are distinct from that forming in response to cold in the WT, 31 but considering that spH2A.W At confers resistance to cold treatment, it might change the adaptative genome control shown previously. 31 It would be interesting to investigate the formation of heterochromatin islands and adaptative response of the genome in cold and other stress conditions conferred by spH2A.W At .…”

Section: H2aw Impacts the Boundary Between Euchromatin And Heterochrmentioning

confidence: 72%

“…These heterochromatin islands are distinct from that forming in response to cold in the WT, 31 but considering that spH2A.W At confers resistance to cold treatment, it might change the adaptative genome control shown previously. 31 It would be interesting to investigate the formation of heterochromatin islands and adaptative response of the genome in cold and other stress conditions conferred by spH2A.W At .…”

Section: H2aw Impacts the Boundary Between Euchromatin And Heterochrmentioning

confidence: 72%

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A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

et al. 2021

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Section: H2aw Impacts the Boundary Between Euchromatin And Heterochrmentioning

confidence: 72%

Section: H2aw Impacts the Boundary Between Euchromatin And Heterochrmentioning

confidence: 72%

A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

et al. 2021

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“…A recent study showed that, despite its presence at DSR genes, Clr4 is not involved in regulating mRNA levels at normal growth temperature, whereas Set1-mediated www.nature.com/scientificreports www.nature.com/scientificreports/ deacetylation by Clr3 and other HDACs plays a key role 52 . However, loss of Clr4 in cells cultivated at 18 °C alters meiotic gene silencing but also the assembly of new facultative heterochromatin islands indicating a critical role for Clr4 at lower temperature 53 . Since Abo1 deletion have been show to affect the global gene expression and nucleosome occupancy in vivo 38 , we cannot rule out the possibility that Abo1 acts across the genome affecting indirectly the gene expression.…”

Section: Discussionmentioning

confidence: 99%

Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin

Dong

Oya

Zahedi

et al. 2020

Sci Rep

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Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled is still unclear. Here, we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining global nucleosome organisation in fission yeast. We identified several key factors involved in heterochromatin silencing that interact genetically with Abo1: histone deacetylase Clr3, H3K9 methyltransferase Clr4, and HP1 homolog Swi6. Cells lacking Abo1 cultivated at 30 °C exhibit an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin has increased H3K9me2 but decreased H3K9me3 levels compared to wild-type. In contrast, facultative heterochromatin regions exhibit reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both the centromeres and subtelomeres, but not in a subset of heterochromatin islands in our condition. Thus, our work uncovers a role of Abo1 in stabilising directly or indirectly Clr4 recruitment to allow the H3K9me2 to H3K9me3 transition in heterochromatin.In eukaryotic cells, the regions of the chromatin that contain active genes are termed euchromatin, and these regions condense in mitosis to allow for chromosome segregation and decondense in interphase to allow for gene transcription 1 . The chromatin regions that remain condensed throughout the cell cycle are defined as heterochromatin regions and are transcriptionally repressed 2,3 . In general, heterochromatin can be defined molecularly by the modification of histone H3, specifically the absence of methylation on lysine 4 (H3K4me) and presence of methylation on lysine 9 (H3K9me) 4-6 . A conserved group of heterochromatin proteins, the heterochromatin protein 1 (HP1) family, specifically recognise heterochromatin regions by binding to H3K9me. Both di-and tri-methylation (H3K9me2/3) enable the binding of HP1 proteins to silence heterochromatin 7,8 . Heterochromatin regions can be further classified into constitutive and facultative heterochromatin 9,10 . Fission yeast, Schizosaccharomyces pombe, is an excellent model organism for chromatin studies because its heterochromatin organisation is similar to human cells 11,12 . Examples of constitutive heterochromatin regions in S. pombe are the pericentromeric regions that contain repetitive DNA sequences 13 . These regions are regulated by RNAi-dependent silencing machinery that involves protein Dcr1 and Ago1 14,15 . In contrast, the silencing of facultative heterochromatin, such as subtelomeric regions and heterochromatin islands, is mediated by RNAi-independent machinery that can be dynamically modulated to express genes required for the cell cycle or adaptation to the cell environment 16,17 . A subset of facultative heterochromatin islands, known as "determinant of selective removal" (DSR) islands, contain meiotic ...

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“…This finding is based on the studies using K∆::ura4 + off allele [75,89]. In addition to ura4 + , ade6 + gene is a widely used reporter in S. pombe for RNAi-dependent and independent heterochromatin formation at centromeric regions and the mating-type locus [29,77,90,91]. When the K region is replaced by an ade6 + reporter gene, the reporter gene can be silenced by heterochromatin (K∆::ade6 + off) [29].…”

Section: The Role Of Lsd Proteins In Maintenance and Re-establishmentmentioning

confidence: 99%

The Catalytic-Dependent and -Independent Roles of Lsd1 and Lsd2 Lysine Demethylases in Heterochromatin Formation in Schizosaccharomyces pombe

Marayati

Tucker

Cerda

et al. 2020

Cells

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In eukaryotes, heterochromatin plays a critical role in organismal development and cell fate acquisition, through regulating gene expression. The evolutionarily conserved lysine-specific demethylases, Lsd1 and Lsd2, remove mono- and dimethylation on histone H3, serving complex roles in gene expression. In the fission yeast Schizosaccharomyces pombe, null mutations of Lsd1 and Lsd2 result in either severe growth defects or inviability, while catalytic inactivation causes minimal defects, indicating that Lsd1 and Lsd2 have essential functions beyond their known demethylase activity. Here, we show that catalytic mutants of Lsd1 or Lsd2 partially assemble functional heterochromatin at centromeres in RNAi-deficient cells, while the C-terminal truncated alleles of Lsd1 or Lsd2 exacerbate heterochromatin formation at all major heterochromatic regions, suggesting that Lsd1 and Lsd2 repress heterochromatic transcripts through mechanisms both dependent on and independent of their catalytic activities. Lsd1 and Lsd2 are also involved in the establishment and maintenance of heterochromatin. At constitutive heterochromatic regions, Lsd1 and Lsd2 regulate one another and cooperate with other histone modifiers, including the class II HDAC Clr3 and the Sirtuin family protein Sir2 for gene silencing, but not with the class I HDAC Clr6. Our findings explore the roles of lysine-specific demethylases in epigenetic gene silencing at heterochromatic regions.

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Iron homeostasis regulates facultative heterochromatin assembly in adaptive genome control

Cited by 33 publications

References 73 publications

A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin

The Catalytic-Dependent and -Independent Roles of Lsd1 and Lsd2 Lysine Demethylases in Heterochromatin Formation in Schizosaccharomyces pombe

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