Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A chemical probe for Tudor domain protein SPIN1 to investigate chromatin functions

ABSTRACT: Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails and in combination with other modifications provide the basis for a combinatorial 'chromatin or histone code'. Recognition of modified histone residues is accomplished in a specific manner by 'reader' domains that recognize chromatin modifications allowing to associate with specific effector complexes mediating chromatin functions. The methyl-lysine and methyl-arginine reader domain protein SPINDLIN1 (SPIN1) belongs to a family of 5 human genes, and has been identified as a putative oncogene and transcriptional co-activator containing three Tudor domains, able to mediate chromatin binding. Here we report on the discovery of the potent and selective bivalent Tudor domain inhibitor VinSPINIn* (see Footnote), which simultaneously engages Tudor domains 1 and 2 and effectively competes with chromatin binding. Inhibitor, chemoproteomic and knockdown studies in squamous cell carcinoma suggest an un-anticipated complexity of SPIN isoform mediated interactions in regulating cellular phenotypes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Andrew Lewis

LAB HEAD: Kilian Huber

PROVIDER: PXD011703 | Pride | 2022-02-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	ChemoproteomicsSummary.xlsx	Xlsx
	HF392_MSQ1470_20180921_AndrewLewis_s1_180921175750.raw	Raw
	HF392_MSQ1470_20180921_AndrewLewis_s2.raw	Raw
	HF392_MSQ1470_20180921_AndrewLewis_s3.raw	Raw
	HF392_MSQ1470_20180921_AndrewLewis_s4.raw	Raw

Items per page:

1 - 5 of 13

Similar Datasets

A chemical probe for Tudor domain protein SPIN1 to investigate chromatin functions

Project description:Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails and in combination with other modifications provide the basis for a combinatorial 'chromatin or histone code'. Recognition of modified histone residues is accomplished in a specific manner by 'reader' domains that recognize chromatin modifications allowing to associate with specific effector complexes mediating chromatin functions. The methyl-lysine and methyl-arginine reader domain protein SPINDLIN1 (SPIN1) belongs to a family of 5 human genes, and has been identified as a putative oncogene and transcriptional co-activator containing three Tudor domains, able to mediate chromatin binding. Here we report on the discovery of the potent and selective bivalent Tudor domain inhibitor VinSPINIn, which simultaneously engages Tudor domains 1 and 2 and effectively competes with chromatin binding. Inhibitor, chemoproteomic and knockdown studies in squamous cell carcinoma suggest an un-anticipated complexity of SPIN isoform mediated interactions in regulating cellular phenotypes.

2018-11-29 | GSE123084 | GEO

TDRD3 is an effector molecule for arginine methylated histone marks

Project description:Specific sites of histone tail methylation are associated with transcriptional activity at gene loci. These methyl-marks are interpreted by effector molecules, which harbor protein domains that bind the methylated motifs and facilitate either active or inactive states of transcription. CARM1 and PRMT1 are transcriptional coactivators that deposit H3R17me2a and H4R3me2a marks, respectively. We used a protein domain microarray approach to identify the tudor domain-containing protein TDRD3 as a “reader” of these marks. Importantly, TDRD3 itself is a transcriptional coactivator. This coactivator activity requires an intact tudor domain. TDRD3 is recruited to an estrogen responsive element in a CARM1-dependent manner. Furthermore, ChIP-seq analysis of TDRD3 reveals that it is predominantly localized to transcriptional start site. Thus, TDRD3 is an effector molecule that promotes transcription by binding methylarginine marks on histone tails. ChIP seq analysis of TDRD3 in MCF7 cells

2011-01-06 | E-GEOD-22612 | biostudies-arrayexpress

SPINDOC promotes genome-wide redistribution of Spindlin1

Project description:Spindlin1 is a histone reader with three Tudor-like domains and its reader activity of histone methylation could be attenuated by SPINDOC. To validate such a role in cellular context, we performed ChIP-Seq in HEK293 cell with SPINDOC overexpressed cell line and control cell line.

2023-11-18 | GSE247551 | GEO

TDRD3 is an effector molecule for arginine methylated histone marks

2011-01-06 | GSE22612 | GEO

Role of the Tudor-knot domain of the TIP60 lysine acetyltransferase [RNA-seq]

Project description:The histone lysine acetyltransferase TIP60 is the main enzyme that catalyzes histone H4 acetylation in cells. Domains on TIP60 regulate its enzymatic activity from different aspects. Here we use a CRISPR-Cas9 tiling screen to scan for essential domains on TIP60 protein and found that the Tudor-knot domain is essential for cell survival and intercellular H4 acetylation. We performed in-vitro biochemical assays and demonstrated Tudor-knot domain is not a histone reader. And deficiency of the Tudor-knot domain has mild effects on TIP60 intracellular localization, as well as the TIP60 complex’s constitution. But Tudor-knot deficiency significantly reduces TIP60 HAT activity both in vivo and in vitro. By comparing the catalytic efficiency of nucleosome substrate and histone octamer substrate, as well as TIP60 protein alone or TIP60 complex, we found the nucleosomal structure and other TIP60 complex components are required for Tudor-knot relative HAT activity regulation. We propose that the Tudor-knot domain function to increase nucleosome accessibility. Finally, we show that the Tudor-knot domain is required for TIP60-dependent transcription regulation. Altogether, our study reveals a mechanism that the Tudor-knot domain that regulates TIP60-dependent transcription through the regulation of TIP60 substrate catalytic efficiency.

2023-12-24 | GSE245115 | GEO

Role of the Tudor-knot domain of the TIP60 lysine acetyltransferase [ChIP-seq]

2023-12-24 | GSE245116 | GEO

ChromID identifies the protein interactome at chromatin marks

Project description:Chromatin modifications instruct genome function through spatiotemporal recruitment of regulatory factors to the genome. However, how these modifications define the proteome composition at distinct chromatin states remains to be fully characterized. Here, we made use of natural protein domains as modular building blocks to develop engineered chromatin readers (eCRs) selective for histone and DNA modifications. By stably expressing eCRs in mouse embryonic stem cells and measuring their subnuclear localisation, genomic distribution and histone-PTM-binding preference, we first demonstrate their applicability as selective chromatin binders in living cells. Finally, we exploit the binding specificity of eCRs to establish ChromID, a new method for chromatin-dependent proteome identification based on proximity biotinylation. We use ChromID to reveal the proteome at distinct chromatin states in mouse stem cells, and by using a synthetic dual-modification reader, we furthermore uncover the protein composition at bivalent promoters marked by H3K4me3 and H3K27me3. These results highlight the applicability of ChromID as novel method to obtain a detailed view of the protein interaction network determined by the chemical language on chromatin.

2020-04-30 | PXD017235 | Pride

Mass spectrometry-based proteomic comparison of BirA-SMN, BirA-SMN-Y109C and BirA proxisomes.

Project description:Although recent advances in gene therapy provide hope for spinal muscular atrophy (SMA) patients, the pathology remains the leading genetic cause of infant mortality. SMA is a monogenic pathology that originates from the loss of the SMN1 gene in most cases or mutations in rare cases. Interestingly, SMN1 mutations occur broadly either within the TUDOR methyl-arginine (Rme) reader domain of SMN or its carboxy terminal oligomerization domain. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a proximity-dependent biotinylation proteomic (BioID) approach, we have identified and validated a number of SMN-interacting proteins, including Fragile X mental retardation family members (FMRFM), such as FMRP itself as well as FXR1 and FXR2, some depending on a wild-type version of the TUDOR domain.

2022-10-19 | PXD030970 | Pride

Nucleosome conformation dictates the histone code

Project description:Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized “codes” that are read by specialized domains (reader domains) in chromatin associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP - histone PTM] specificity, and in doing so to decipher the histone code. However, this has largely been done using a reductive approach of isolated reader domains and histone peptides, with the assumption that PTM readout is unaffected by any higher order considerations. Here we show that histone PTM specificity is in fact dependent on nucleosomal context, necessitating we re-define the ‘histone code’ concept and further interrogate it at the nucleosomal level.

2021-05-06 | GSE150617 | GEO

SART3 is a Novel Rme2s Reader studied by tandem MS

Project description:Arginine methylation is a ubiquitous post-translational modification involved in many biological processes such as transcription, cell signaling and RNA splicing. Tudor domains by far are the major effector domain family for arginine methylation mark recognition. Here we characterize SART3 as a novel selective reader for symmetric dimethylarginine (Rme2s) marks. SART3 harbors a series of HAT (Half-a-TPR) repeats that are aromatic-rich, and it is this region that binds Rme2s motifs. An analysis of the reported structure of the HAT repeats of SART3 identified a putative aromatic cage that potentially “read” the Rme2s-modified motifs, and the key aromatic residues required for Rme2s recognition were identified. We further confirm that this Rme2s reader ability is important for SART3-mediated RNA splicing. Together, our studies revealed that the evolutionarily conserved SART3 HAT domain was a novel reader of Rme2s mark involved in RNA splicing.

2024-10-17 | PXD046708 | Pride