NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes

Fei, Jia; Ishii, Haruhiko; Hoeksema, Marten A.; Meitinger, Franz; Kassavetis, George A.; Glass, Christopher K.; Ren, Bing; Kadonaga, James T.

doi:10.1101/gad.313973.118

Cited by 40 publications

(43 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, GLYR1 downregulation was also found to reduce the sensitivity of CRC cells to 5-FU. However, Fei et al reported that GLYR1 knockout prolonged the G1 phase and inhibited growth of HeLa cells [55], which was contrary to our results. This discrepancy may be because of the different cell lines used in our study and the function of GLYR1 may be influenced by the heterogeneity of tumors.…”

Section: Discussioncontrasting

confidence: 99%

Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways

Long

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background: GLYR1 has a high mutation frequency in microsatellite instability colorectal cancer (MSI CRC) and is presumed to be a novel tumor suppressor. However, the role of GLYR1 in tumors has never been studied. In particular, the downregulation of GLYR1 in MSI CRC is worthy of further investigation. Methods: Western blot and immunohistochemistry analyses were used to detect GLYR1 protein expression in CRC tissues and cell lines, and the clinical significance of GLYR1 was also analyzed. The relationship between GLYR1 and MLH1 was validated by immunofluorescence, immunoprecipitation and bioinformatics analyses. Western blotting, qRT-PCR, CCK-8 assays, colony formation assays, flow cytometry and Hoechst 33258 staining assays were used to assess the effect of GLYR1 on the cell cycle progression, proliferation, differentiation and apoptosis of CRC cells in vitro. The related mechanisms were initially investigated by Western blotting. Results: GLYR1 was significantly downregulated in MSI CRC and its expression was negatively correlated with tumor size and positively correlated with tumor differentiation in CRC patients. In addition, GLYR1 interacted with MLH1 to regulate its nuclear import and expression. Moreover, downregulation of GLYR1 accelerated G1/S phase transition, promoted proliferation and inhibited differentiation of SW480 and SW620 cells in vitro. Furthermore, downregulation of GLYR1 decreased the sensitivity to 5-fluorouracil (5-FU) by inhibiting the mitochondrial apoptosis pathway in CRC cells. Inhibition of the p38 mitogen-activated protein kinase (p38MAPK) and activation of the phosphatidyl 3-kinase/protein kinase B (PI3K/Akt) signaling pathways were involved in the mechanism by which GLYR1 downregulated p21. Conclusions: Ours is the first study to elucidate the role of GLYR1 in tumors and provide evidence for GLYR1 as a biological marker that reflects the degree of malignancy and sensitivity to 5-FU in MSI CRC.

show abstract

Section: Discussioncontrasting

confidence: 99%

Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways

Long

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…First, we designed nucleosome substrates with linker DNA ends blocked by two different end-blocking strategies: the Lac repressor R3 system and the streptavidin-biotin system. Finally, to further test whether Rhp26 is able to disassemble nucleosomes from the nucleosomal array, we used a nucleosome array with a circular plasmid (42). We obtained similar results from all three systems, which are summarized below.…”

Section: Distinct Functions Of Rhp26 C-terminal Region a And Region Bmentioning

confidence: 70%

“…To further test whether Rhp26 is able to disassemble nucleosomes from the nucleosome array, we assembled chromatin on circular DNA using a salt dialysis method and then tested Rhp26's effect on the topology of DNA supercoiling in the nucleosome (42). In the presence of ATP, but not UTP, treatment with the active form of Rhp26 17-910 and topoisomerase I (Topo I) decreased the superhelicity of nucleosomal structures on plasmid DNA in a dose-dependent manner ( Fig.…”

Section: Distinct Functions Of Rhp26 C-terminal Region a And Region Bmentioning

confidence: 99%

Molecular basis of chromatin remodeling by Rhp26, a yeast CSB ortholog

Wang

Limbo

et al. 2019

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

Self Cite

View full text Add to dashboard Cite

CSB/ERCC6 belongs to an orphan subfamily of SWI2/SNF2-related chromatin remodelers and plays crucial roles in gene expression, DNA damage repair, and the maintenance of genome integrity. The molecular basis of chromatin remodeling by Cockayne syndrome B protein (CSB) is not well understood. Here we investigate the molecular mechanism of chromatin remodeling by Rhp26, a Schizosaccharomyces pombe CSB ortholog. The molecular basis of chromatin remodeling and nucleosomal epitope recognition by Rhp26 is distinct from that of canonical chromatin remodelers, such as imitation switch protein (ISWI). We reveal that the remodeling activities are bidirectionally regulated by CSB-specific motifs: the N-terminal leucine-latch motif and the C-terminal coupling motif. Rhp26 remodeling activities depend mainly on H4 tails and to a lesser extent on H3 tails, but not on H2A and H2B tails. Rhp26 promotes the disruption of histone cores and the release of free DNA. Finally, we dissected the distinct contributions of two Rhp26 C-terminal regions to chromatin remodeling and DNA damage repair.chromatin remodeling | histone tail | SNF2-like family ATPase | Cockayne syndrome B | nucleosome sliding and eviction

show abstract

“…NDF (nucleosome destabilizing factor) which was found associated with JIL-1 by mass spectrometry after cross-linking 50 was also enriched (Fig.7a). NDF has recently been shown to destabilize nucleosomes in front of the transcribing polymerase, but its depletion had only minor effects on overall transcript levels 51 . We speculated that the JJ-complex and NDF may have redundant functions on transcription.…”

Section: Resultsmentioning

confidence: 99%

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

Albig

Wang

Dann

et al. 2019

Preprint

View full text Add to dashboard Cite

31In flies, the chromosomal kinase JIL-1 is responsible for most interphase histone H3S10 32 phosphorylation and has been proposed to protect active chromatin from acquiring 33 heterochromatic marks, like dimethylated histone H3K9 (H3K9me2) and HP1. Here, we show 34 that JIL-1's targeting to chromatin depends on a new PWWP domain-containing protein 35JASPer (JIL-1 Anchoring and Stabilizing Protein). The JASPer-JIL-1 (JJ)-complex is the 36 major form of the kinase in vivo and is targeted to active genes and telomeric transposons 37 via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes. Put in place, the 38 complex modulates the transcriptional output. JIL-1 and JJ-complex depletion in cycling cells 39 lead to small changes in H3K9me2 distribution at active genes and telomeric transposons. 40Finally, we identified many new interactors of the endogenous JJ-complex and propose that 41 JIL-1 not only prevents heterochromatin formation, but also coordinates chromatin-based 42 regulation in the transcribed part of the genome. 43 Key Words: PWWP domain / histone phosphorylation / COMPASS / heterochromatin / BOD1 44 / Dpy-30L1 / Telomeres 45 46 Main text 47In mammals, several nuclear kinases contribute to phosphorylation of histone H3 at serine 48 10 (H3S10ph) in interphase, whereas in Drosophila melanogaster, the essential kinase JIL-1 49 is responsible for most of it 1 . The significance of interphase H3S10ph is often 50 underestimated because most H3S10 phosphorylation in asynchronous cell populations 51 stems from mitotic chromatin, where it is deployed by Aurora kinase B 2,3 . Originally, 52interphase H3S10ph has been associated, in combination with H3K9ac and H3K14ac, with 53 transcriptional activation of immediate early genes upon MAPK activation 4,5 . In Drosophila, 54interphase H3S10ph is enriched at the body of active genes 6 . In mammal, in the extreme 55 case of mouse embryonic stem cells (mESC), ~30% of the genome is enriched for H3S10ph 56 in interphase 7 . 57The current model is that JIL-1 protects euchromatin from heterochromatization 8 . According 58 to the phospho-methyl switch model for mitotic H3S10ph 9 , placing H3S10ph prevents H3K9 59 methylation and subsequent binding of heterochromatin components. JIL-1 phosphorylates 60 various H3 peptides with different methylation states, including H3K9me2/3, with a 61 comparable efficiency 6 , whereas histone methyltransferases of the Su(var)3-9 family are 62 inhibited by H3S10ph 10,11 . Several observations suggest that JIL-1 is important for the 63 balance between eu-and heterochromatin. The Su(var)3-1 alleles of JIL-1 gene, which lead 64 to the expression of JIL-1 truncated in its C-terminal domain (CTD), result in reduced 65 heterochromatin spreading at euchromatin-heterochromatin boundaries 12,13 . Conversely, in 66 the JIL-1 z2/z2 null mutant, heterochromatin components spread into euchromatin. The 67 spreading of H3K9me2 and HP1 is highest on the euchromatic part of the X chromosome in 68 both sexes 14 , the spreading of the 7-zinc-finger pr...

show abstract

NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes

Cited by 40 publications

References 50 publications

Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways

Downregulation of GLYR1 contributes to microsatellite instability colorectal cancer by targeting p21 via the p38MAPK and PI3K/AKT pathways

Molecular basis of chromatin remodeling by Rhp26, a yeast CSB ortholog

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

Contact Info

Product

Resources

About