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Record W2987573161 · doi:10.1101/820647

Structural basis for the binding selectivity of human CDY chromodomains

2019· preprint· en· W2987573161 on OpenAlexafffund
Dong Cheng, Yanli Liu, Tian‐Jie Lyu, Serap Beldar, Kelsey N. Lamb, W. Tempel, Yanjun Li, Zoey Li, Lindsey I. James, Qin Su, Yun Wang, Jinrong Min

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsStructural Genomics ConsortiumUniversity of Toronto
FundersNational Institute on Drug AbuseNatural Sciences and Engineering Research Council of CanadaPeking UniversityMinistry of Education, IndiaTsinghua UniversityDirectorate for Biological SciencesNational Institutes of HealthOntario Ministry of Research, Innovation and ScienceOntario GenomicsFundação de Amparo à Pesquisa do Estado de São PauloGenome CanadaBiological and Environmental ResearchNational Natural Science Foundation of ChinaUniversity of ChicagoPfizerNovartis PharmaOntario Genomics InstituteCentral China Normal UniversityEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaAArgonne National LaboratoryUniversity of North Carolina at Chapel HillU.S. Department of Energy
KeywordsChromodomainHistoneLysineHeterochromatin protein 1Histone H3Structural motifEpigeneticsBiologyChemistryComputational biologyGeneticsChromatinCell biologyBiochemistryGeneAmino acidHeterochromatin

Abstract

fetched live from OpenAlex

Abstract The CDY (Chromodomain on the Y) family is a small family of chromodomain containing proteins, whose chromodomains closely resemble those in HP1 and Polycomb. The CDY proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. Based on our structural, binding and mutagenesis data, we synthesized a more CDYL1/2 selective peptidic ligand UNC4850. Our work provides critical implications that CDYL1b’s role in the regulation of neural development is dependent on its recognition of lysine-methylated ARKS motifs.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.229
Teacher spread0.217 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2019
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicGenomics and Chromatin Dynamics→French-language works237,207→