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Selective identification of epigenetic regulators at methylated genomic sites

ABSTRACT: We applied SelectID coupled with the ultra-sensitive micro-DIA approach to enrich the associated proteins of Chromosome 9 satellite region and methylated LINE-1 elements.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hong Wang

PROVIDER: PXD061627 | iProX | Sat Mar 08 00:00:00 GMT 2025

REPOSITORIES: iProX

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Selective identification of epigenetic regulators at methylated genomic sites by SelectID.

Qian Wenchang W Jiang Penglei P Niu Mingming M Fu Yujuan Y Huang Deyu D Zhang Dong D Liang Ying Y Wang Qiwei Q Han Yingli Y Zeng Xin X Shi Yixin Y Jiang Lingli L Yu Zebin Z Li Jinxin J Lu Huan H Wang Hong H Chen Baohui B Qian Pengxu P

Nature communications 20250418 1

DNA methylation is a significant component in proximal chromatin regulation and plays crucial roles in regulating gene expression and maintaining the repressive state of retrotransposon elements. However, accurate profiling of the proteomics which simultaneously identifies specific DNA sequences and their associated epigenetic modifications remains a challenge. Here, we report a strategy termed SelectID (selective profiling of epigenetic control at genome targets identified by dCas9), which intr ...[more]

PMID: 40251151

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Selective identification of epigenetic regulators at methylated genomic sites by SelectID

Project description:Identification and quantification of biotinylated proteins enriched by the Sp-system at Chromosome 9 Satellite regions using TMT-labeled quantitative mass spectrometry

2025-03-05 | PXD061483 |

Selective identification of epigenetic regulators at methylated genomic sites by SelectID [ChIP-seq]

Project description:DNA methylation is a significant component in proximal chromatin regulation and plays crucial roles in regulating gene expression and maintaining the repressive state of retrotransposon elements. However, accurate profiling of the proteomics which simultaneously identifies specific DNA sequences and their associated epigenetic modifications remains a challenge. Here, we report SelectID, which introduced methylated DNA binding domain into dCas9-mediated proximity labeling system to enable in situ protein capture at repetitive elements with 5-methylcytosine (5mC) modifications. SelectID were demonstrated as feasible as dCas9-TurboID system at specific DNA methylation regions, such as the chromosome 9 satellite. Using SelectID, we successfully identified CHD4 as potential repressors of methylated LINE-1 retrotransposon through direct binding at the 5’UTR of young LINE-1 elements. Overall, our SelectID approach has opened up new avenues for uncovering potential regulators of specific DNA regions with DNA methylation, which will greatly facilitate future studies on epigenetic regulation.

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Selective identification of epigenetic regulators at methylated genomic sites by SelectID [ChIP-seq]

Project description:Selective identification of epigenetic regulators at methylated genomic sites by SelectID [ChIP-seq]

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Project description:Selective identification of epigenetic regulators at methylated genomic sites by SelectID [RNA-seq]

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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

Project description:The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity.

2019-09-12 | PXD014829 | Pride

DOT1L regulates pericentromeric heterochromatin

Project description:Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.

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Genomic characterization of five commonly used endometrial cancer cell lines

Project description:An in-depth examination of five endometrial cancer cell lines in which mutation profiles, copy number variation, micro-satellite instability and homolgous recombination repair ability were determined and assessed in the context of TCGA endometrial cancer groups.

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Study of Intratumoral IVX037 in Patients With Advanced or Metastatic Solid Tumours

Project description:This is a Phase 1 open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in people with micro satellite-stable (MSS) colorectal or gastroesophageal cancer metastatic to liver, or advanced ovarian cancer.

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Genomic and genetic characterization of rice Cen3 reveals evolutionary remnants of a complex centromere (mRNA data)

Project description:The centromere is the chromosomal site for assembly of the kinetochore where spindle fibers attach during cell division. In most muticellular eukaryotes, centromeres are composed of long tracks of satellite repeats that are recalcitrant to sequencing and fine scale genetic mapping. Here we report the genomic and genetic characterization of the complete centromere of rice chromosome 3. Using a DNA fiber-fluorescence in situ hybridization approach, we demonstrated that the centromere of chromosome 3 (Cen3) contains ~414 kb of the centromeric satellite repeat CentO. Cen3 includes a ~1,851-kb domain associated with CENH3, the centromere-specific histone H3 variant. This CENH3-associated chromatin domain is embedded within a 3,083-kb region that lacks genetic recombination. We detected several active genes within the CENH3-binding domain based on a comprehensive annotation and a survey for matches with mRNA signatures. However, the gene density in the CENH3-binding domain is significantly lower than in the pericentromeric domains. In contrast, the CENH3-binding domain contains a higher percentage of repetitive DNA sequences than the pericentromeric regions. These results suggest that Cen3 is in the process of evolving from a genic region toward an accumulation of satellite repeats and transposable elements that is more characteristic of centromeres in most complex eukaryotic species. MPSS was performed to sequence small RNAs that derived from 16 untreated and 6 abiotic-treated diverse tissue libraries. The method for the MPSS sequencing of mRNAs is described in Brenner et al. (Nat Biotechnol. 2000 18:630).

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