The Mediator complex as a master regulator of transcription by RNA polymerase II

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(11), С. 732 - 749

Опубликована: Июнь 20, 2022

Язык: Английский

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Functional partitioning of transcriptional regulators by patterned charge blocks

Cell, Год журнала: 2023, Номер 186(2), С. 327 - 345.e28

Опубликована: Янв. 1, 2023

Язык: Английский

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Deciphering the multi-scale, quantitative cis-regulatory code

Molecular Cell, Год журнала: 2023, Номер 83(3), С. 373 - 392

Опубликована: Янв. 23, 2023

Uncovering the cis-regulatory code that governs when and how much each gene is transcribed in a given genome cellular state remains central goal of biology. Here, we discuss major layers regulation influence transcriptional outputs are encoded by DNA sequence context. We first transcription factors bind specific sequences dosage-dependent cooperative manner then proceed to cofactors facilitate factor function mediate activity modular elements such as enhancers, silencers, promoters. consider complex poorly understood interplay these diverse within regulatory landscapes its relationships with chromatin states nuclear organization. propose mechanistically informed, quantitative model integrates multiple will be key ultimately cracking code.

Язык: Английский

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Generating specificity in genome regulation through transcription factor sensitivity to chromatin

Nature Reviews Genetics, Год журнала: 2022, Номер 23(12), С. 728 - 740

Опубликована: Июль 12, 2022

Язык: Английский

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Large-scale mapping and mutagenesis of human transcriptional effector domains

Nature, Год журнала: 2023, Номер 616(7956), С. 365 - 372

Опубликована: Апрель 5, 2023

Язык: Английский

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“Structure”-function relationships in eukaryotic transcription factors: The role of intrinsically disordered regions in gene regulation

Molecular Cell, Год журнала: 2022, Номер 82(21), С. 3970 - 3984

Опубликована: Окт. 19, 2022

Язык: Английский

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CRISPR technologies for genome, epigenome and transcriptome editing

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(6), С. 464 - 487

Опубликована: Фев. 2, 2024

Язык: Английский

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A universal deep-learning model for zinc finger design enables transcription factor reprogramming

Nature Biotechnology, Год журнала: 2023, Номер 41(8), С. 1117 - 1129

Опубликована: Янв. 26, 2023

Cys2His2 zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, structurally intricate engagement ZF DNA has made their design challenging. Here we describe screening 49 billion protein-DNA interactions and development a deep-learning model, ZFDesign, that solves any genomic target. ZFDesign is modern machine learning method models global target-specific differences induced by range library environments specifically takes into account compatibility neighboring fingers using novel hierarchical transformer architecture. We demonstrate versatility designed ZFs as nucleases well activators repressors seamless reprogramming human transcription factors. These factors could be used upregulate allele haploinsufficiency, downregulate gain-of-function mutation or test consequence single opposed genes factor would normally influence.

Язык: Английский

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Hold out the genome: a roadmap to solving the cis-regulatory code

Nature, Год журнала: 2023, Номер 625(7993), С. 41 - 50

Опубликована: Дек. 13, 2023

Язык: Английский

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Proteome-scale discovery of protein degradation and stabilization effectors

Nature, Год журнала: 2024, Номер 628(8009), С. 878 - 886

Опубликована: Март 20, 2024

Язык: Английский

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