Engineering intrinsically disordered regions (IDRs) for guiding genome navigation
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE290820 | GEO | 2026/02/14
REPOSITORIES: GEO
Similar Datasets
Project description:Engineering intrinsically disordered regions (IDRs) for guiding genome navigation
| PRJNA1230175 | ENA
Project description:Profiling Msn2 IDR sequence variants to reveal the grammar underlying specificity
2023-04-20 | GSE212466 | GEO
Project description:Intrinsically disordered regions (IDRs) are abundant within eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as exemplified by the budding-yeast TF- Msn2. To examine how low-complexity IDRs encode multiple functions, we compared genomic binding preferences, gene induction, and coactivator recruitment amongst a large set of designed Mns2-IDR mutants. We show that multiple regions across the >500AA IDR contribute to both functions. Yet, transcription activity was readily disrupted by variants having no consequences on Msn2 binding. Our data attribute this differential sensitivity to the integration of relaxed, composition-based code directing binding preferences with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Interwoven sequence grammar may present a general paradigm through which low-complexity IDRs encode multiple functions.
2023-11-19 | GSE239883 | GEO
Project description:Intrinsically disordered regions (IDRs) are abundant within eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as exemplified by the budding-yeast TF- Msn2. To examine how low-complexity IDRs encode multiple functions, we compared genomic binding preferences, gene induction, and coactivator recruitment amongst a large set of designed Mns2-IDR mutants. We show that multiple regions across the >500AA IDR contribute to both functions. Yet, transcription activity was readily disrupted by variants having no consequences on Msn2 binding. Our data attribute this differential sensitivity to the integration of relaxed, composition-based code directing binding preferences with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Interwoven sequence grammar may present a general paradigm through which low-complexity IDRs encode multiple functions.
2023-11-19 | GSE239882 | GEO
Project description:Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. While sequence-specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. Unexpectedly, a binding motif essential in the wild- type IDR can be removed when compensatory changes to the sequence chemistry are introduced, highlighting the orthogonality and interoperability of these properties and expanding the sequence space compatible with function. Our results provide a general framework for the functional constraints on IDR evolution.
2025-12-17 | GSE314049 | GEO
Project description:In eukaryotes, the hetero-hexameric origin recognition complex (ORC) is responsible for assembling Mcm2-7 complex into a head-to-head double hexamer (DH), forming pre-replicative complex (pre-RC) that licenses origin DNA for replication initiation. This process is tightly controlled throughout the cell cycle to ensure accurate duplication of the genome. Here we show that the N-terminal intrinsically disordered region (IDR) of the yeast Orc2 subunit plays a critical role in promoting pre-RC assembly. We found that removing a short segment (residues 175-200) from Orc2-IDR or mutating a key isoleucine (194) in this region significantly inhibits replication initiation across the genome and causes cell death. Although the Orc2-IDR mutants can still assemble the ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate on DNA, the assembled mutant OCCM exhibits impaired ATP hydrolysis, preventing its conversion into Mcm2-7-ORC (MO) complex and subsequent DH formation. Interestingly, our in vitro assays showed that adding the Orc2-IDR peptide in the pre-RC reactions can rescue this defect. Furthermore, phosphorylation of this Orc2-IDR motif by S-cyclin dependent kinase (S-CDK) blocks its binding to Mcm2, leading to defective pre-RC assembly. Our findings provide crucial mechanistic insights into the multifaceted roles of ORC in modulating MCM loading to support origin licensing during the G1 phase and its regulation to restrict origin firing within the S phase.
2024-09-18 | GSE262693 | GEO
Project description:Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. While sequence-specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. Unexpectedly, a binding motif essential in the wild- type IDR can be removed when compensatory changes to the sequence chemistry are introduced, highlighting the orthogonality and interoperability of these properties and expanding the sequence space compatible with function. Our results provide a general framework for the functional constraints on IDR evolution.
2025-12-17 | GSE314051 | GEO
Project description:Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. While sequence-specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. Unexpectedly, a binding motif essential in the wild- type IDR can be removed when compensatory changes to the sequence chemistry are introduced, highlighting the orthogonality and interoperability of these properties and expanding the sequence space compatible with function. Our results provide a general framework for the functional constraints on IDR evolution.
2025-12-17 | GSE314050 | GEO
Project description:As a transcriptional coactivator, SPIN1 has been reported to bind to chromatin.To assess the effect of IDR on chromatin binding, we investigated genome-wide chromatin association of SPIN1-WT or SPIN1-△IDR stably overexpressed cell lines by chromatin immunoprecipitation followed by high-throughput sequencing.
2024-12-19 | GSE215398 | GEO
Project description:Intrinsically disordered regions (IDRs) are well-known facilitators of chromatin regulation, but their role as regulatory restraints remains underexplored. Here, we reveal that the C-terminal IDR of mammalian ALKBH5 anchors its main activity to mRNA, limiting chromatin engagement in mouse embryonic stem cells (mESCs). IDR deletion redirects ALKBH5 to chromatin-associated non-coding RNAs, driving widespread chromatin opening and transcriptional activation. This mechanism extends to histone demethylases, where IDR deletion also results in broad removal of repressive histone marks, leading to increased chromatin accessibility and activation of transposable elements. Leveraging these insights, we engineered ALKBH5 and its plant homologs with IDR deletion. Overexpression of these IDR-deleted ALKBH5 demethylases could promote Arabidopsis root growth and increase rice yield. Our findings uncover a conserved role for IDRs in restraining chromatin access by RNA and histone demethylases and establish a new strategy of chromatin programming for crop engineering using plant proteins.
2026-03-09 | GSE286066 | GEO