Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

Wang, Jiyong; Tadeo, Xavier; Hou, Haitong; Tu, Patricia G.; Thompson, James; Yates, John R.; Jia, Songtao

doi:10.1101/gad.221010.113

Cited by 66 publications

(96 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Curiously, H4K16ac is similarly enriched at promoters and enhancers of embryonic stem cells (Taylor et al 2013), which have been previously suggested to contain especially dynamic chromatin (Meshorer et al 2006). H4K16ac has been reported to counter heterochromatin spreading (Wang et al 2013). Conceivably, H4K16ac constitutes a local chromatin ''barrier'' to prevent promoter silencing in unusual chromatin environments in embryonic stem cells and senescent cells.…”

Section: Discussionmentioning

confidence: 99%

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

et al. 2014

View full text Add to dashboard Cite

Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogeneinduced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression.

show abstract

Section: Discussionmentioning

confidence: 99%

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In addition, exogenously introduced siRNAs fail to establish heterochromatin unless Swi6 is overexpressed (Iida et al 2008). Moreover, overexpression of Swi6 increases the conversion rate of a less stable heterochromatin domain at the mating type region (Nakayama et al 2000) and enhances the spreading of heterochromatin when chromatin boundaries are compromised (Noma et al 2001;Wang et al 2013). Thus, the multiple pathways that regulate heterochromatin assembly at constitutive heterochromatin regions, such as telomeric, pericentric, and the silent mating type regions, might be key to the formation of higher-affinity platforms for heterochromatin proteins, thus balancing the need for proper heterochromatin assembly at these regions and preventing heterochromatin assembly at cryptic sites.…”

Section: Discussionmentioning

confidence: 99%

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

Self Cite

View full text Add to dashboard Cite

The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed to pericentric regions through RNAiindependent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation.

show abstract

“…As is true for human KDM5A (Nishibuchi et al 2014), Msc1 associates with HDAC activity (Ahmed et al 2004), although there is no evidence to date indicating that Msc1 exists in a stable physical complex with purified fission yeast HDACs Clr6, Clr3, and Sir2 (Nicolas et al 2007;Sugiyama et al 2007;Buchanan et al 2009;Wang et al 2013;Zilio et al 2014). Further suggesting a role for Msc1 in chromatin biology, Msc1 has been found consistently as a component of the fission yeast Swr1C complex (Buchanan et al 2009;Kim et al 2009;Zofall et al 2009;Hou et al 2010;Qiu et al 2010), which facilitates the exchange of histone H2A.Z for H2A at specific chromosomal locations.…”

Section: Discussionmentioning

confidence: 99%

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

George

Walworth

2015

Genetics

View full text Add to dashboard Cite

Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis. Genetic analysis implicates a histone deacetylase (HDAC)-linked pathway in suppression because HDAC mutants clr6-1, clr3D, and sir2D, though not hos2D, also promote normal mitosis in the dis1-288 mutant. Suppression of the dis phenotype through loss of msc1 function requires the spindle checkpoint protein Mad2 and is limited by the presence of the heterochromatin-associated HP1 protein homolog Swi6. We speculate that alterations in histone acetylation promote a centromeric chromatin environment that compensates for compromised dis1 function by allowing for successful kinetochore-microtubule interactions that can satisfy the SAC. In cells arrested in mitosis by mutation of dis1, loss of function of epigenetic determinants such as Msc1 or specific HDACs can promote cell survival. Because the KDM5 family of proteins has been implicated in human cancers, an appreciation of the potential role of this family of proteins in chromosome segregation is warranted. KEYWORDS Msc1; lysine demethylase KDM5; histone deacetylase (HDAC); Rb; PLU-1; RBP2; trichostatin; thiabendazole; Mad2; Dis1 (XMAP215, TOG1); Swi6 (HP1 homolog) A CCURATE chromosome segregation relies on precise assembly of the multiprotein kinetochore complex, which mediates the link between chromosomes and the mitotic spindle (Przewloka and Glover 2009). The histone H3 variant CENP-A, along with epigenetic marks on canonical histones, defines centromeric chromatin, which forms the template for kinetochore assembly (Allshire and Karpen 2008;Verdaasdonk and Bloom 2011). Kinetochores serve as the site of spindle microtubule attachment (Santaguida and Musacchio 2009) and, along with the centromere, translate microtubule attachment status to mediate force balance, tension sensing, and spindle checkpoint control (Bloom 2014). When associations between chromosomes and the spindle are incorrect, the spindle assembly checkpoint (SAC) delays progression through mitosis by preventing the onset of anaphase (Musacchio and Salmon 2007;Foley and Kapoor 2013).Fission yeast centromeric chromatin (Allshire and Ekwall 2015) consists of a central core (cnt) and internal inverted repeats (imr), defined by the presence of CENP-A and methylated histone H3 K4 chromatin, flanked by heterochromatic outer repeats (otr) marked by methylated histone H3 K9 (Partridge et al. 2000;Takahashi et al. 2000;Kniola et al. 2001). The consti...

show abstract

Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

Cited by 66 publications

References 91 publications

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

Contact Info

Product

Resources

About