Elimination of a specific histone H3K14 acetyltransferase complex bypasses the RNAi pathway to regulate pericentric heterochromatin functions

Reddy, Bharat; Wang, Yu; Niu, Lifang; Higuchi, Emily C.; Marguerat, Samuel; Bähler, Jürg; Smith, Gerald R.; Jia, Songtao

doi:10.1101/gad.1993611

Cited by 59 publications

(88 citation statements)

References 41 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1C; Supplemental Table S1). Our screen identified mutants known to bypass RNAi for pericentric heterochromatin assembly, such as Mst2 complex components mst2D, nto1D, and ptf2D (Reddy et al 2011;Wang et al 2012), validating the effectiveness of our screen. Our screen also identified poz1D, a telomere shelterin component involved in telomere length control (Miyoshi et al 2008), as showing the strongest rescue of heterochromatic silencing (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 79%

“…Antibodies used were H3K9me2 (Abcam), Swi6 (Reddy et al 2011), Pol II (Covance), myc (Covance), and Flag (Sigma). Quantitative real-time PCR (qPCR) was performed with Maxima SYBR Green qPCR master mix (Fermentas) in an ABI 7300 RealTime PCR System.…”

Section: Chip Analysismentioning

confidence: 99%

“…The concentration of each target gene in wild type was arbitrarily set to 1 and served as reference for other samples. Northern blot of siRNAs was performed as described previously (Reddy et al 2011).…”

Section: Rna Analysesmentioning

confidence: 99%

“…Interestingly, elimination of the Mst2 histone H3K14 acetyltransferase complex activity, the JmjC domain protein Epe1, or RNA quality control factor Mlo3 bypasses the requirement of RNAi for pericentric heterochromatin assembly (Trewick et al 2007;Reddy et al 2011;ReyesTurcu et al 2011). Although the mechanisms by which these mutants regulate heterochromatin assembly in the absence of RNAi differ, these results nonetheless indicate that RNAi is not obligatory for pericentric heterochromatin formation under certain conditions.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

Section: Resultsmentioning

confidence: 79%

Section: Chip Analysismentioning

confidence: 99%

Section: Rna Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Antibodies used were H3K9me2 (Abcam, ab1220), H4K16ac (Active Motif, 39167), H3 (Abcam, ab1791), H4 (Abcam, ab10158), and Flag (Sigma, A2220). Swi6 antibody was custom-made with full-length recombinant Swi6 protein and affinity-purified (Reddy et al 2011).…”

Section: Chip Analysismentioning

confidence: 99%

Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

et al. 2013

Self Cite

View full text Add to dashboard Cite

Heterochromatin spreading leads to the silencing of genes within its path, and boundary elements have evolved to constrain such spreading. In fission yeast, heterochromatin at centromeres I and III is flanked by inverted repeats termed IRCs, which are required for proper boundary functions. However, the mechanisms by which IRCs prevent heterochromatin spreading are unknown. Here, we identified Bdf2, which is homologous to the mammalian bromodomain and extraterminal (BET) family double bromodomain proteins involved in diverse types of cancers, as a factor required for proper boundary function at IRCs. Bdf2 is enriched at IRCs through its interaction with the boundary protein Epe1. The bromodomains of Bdf2 recognize acetylated histone H4 tails and antagonize Sir2-mediated deacetylation of histone H4K16. Furthermore, abolishing H4K16 acetylation (H4K16ac) with an H4K16R mutation promotes heterochromatin spreading, and mimicking H4K16ac by an H4K16Q mutation blocks heterochromatin spreading at IRCs. Our results thus illustrate a mechanism of establishing chromosome boundaries at specific sites through the recruitment of a factor that protects euchromatic histone modifications. They also reveal a previously unappreciated function of H4K16ac in cooperation with H3K9 methylation to regulate heterochromatin spreading.

show abstract

Regulation of centromeric heterochromatin in the cell cycle by phosphorylation of histone H3 tyrosine 41

Ren

Chen

2019

Curr Genet

View full text Add to dashboard Cite

Elimination of a specific histone H3K14 acetyltransferase complex bypasses the RNAi pathway to regulate pericentric heterochromatin functions

Cited by 59 publications

References 41 publications

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

Regulation of centromeric heterochromatin in the cell cycle by phosphorylation of histone H3 tyrosine 41

Contact Info

Product

Resources

About