The N-Terminal Part of Drosophila CP190 Is a Platform for Interaction with Multiple Architectural Proteins DOI Open Access
А. К. Головнин,

L. S. Melnikova,

Valentin Babosha

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(21), С. 15917 - 15917

Опубликована: Ноя. 2, 2023

CP190 is a co-factor in many Drosophila architectural proteins, being involved the formation of active promoters and insulators. contains N-terminal BTB/POZ (Broad-Complex, Tramtrack Bric brac/POxvirus Zinc finger) domain adjacent conserved regions protein interactions. Here, we examined functional roles these domains vivo. The best-characterized proteins with insulator functions, Pita, Su(Hw), dCTCF, interacted predominantly BTB CP190. Due to difficulty mutating domain, obtained transgenic line expressing chimeric human Kaiso. Another group M1BP, Opbp, ZIPIC, one or both highly part Transgenic lines D. melanogaster mutants deletion each were obtained. results showed that mutant only partially compensated for functions CP190, weakly binding selective chromatin sites. Further analysis confirmed essential role recruitment regulatory associated proteins. We also found was sufficient recruiting Z4 Chromator successfully achieving opening. Taken together, our previous studies region platform simultaneous interaction various DNA-binding transcription complexes.

Язык: Английский

3D Enhancer–promoter networks provide predictive features for gene expression and coregulation in early embryonic lineages DOI
Dylan Murphy, Eralda Salataj, Dafne Campigli Di Giammartino

и другие.

Nature Structural & Molecular Biology, Год журнала: 2023, Номер 31(1), С. 125 - 140

Опубликована: Дек. 5, 2023

Язык: Английский

Процитировано

20
Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation DOI Creative Commons
Aditi Chandra, Sora Yoon, Michaël F. Michieletto

и другие.

Immunity, Год журнала: 2023, Номер 56(7), С. 1451 - 1467.e12

Опубликована: Май 31, 2023

Язык: Английский

Процитировано

17
An integrated view of the structure and function of the human 4D nucleome DOI Creative Commons
Job Dekker,

Betul Akgol Oksuz,

Yang Zhang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 19, 2024

Abstract The dynamic three-dimensional (3D) organization of the human genome (the “4D Nucleome”) is closely linked to function. Here, we integrate a wide variety genomic data generated by 4D Nucleome Project provide detailed view 3D in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We extensive benchmarking mapping assays these diverse datasets annotate spatial features across scales. reveal rich complexity chromatin domains their sub-nuclear positions, over one hundred thousand structural loops promoter-enhancer interactions. developed models population-based individual cell-to-cell variation structure, establishing connections between chromosome folding, nuclear organization, looping, gene transcription, DNA replication. demonstrate use computational methods predict folding from sequence, uncovering potential effects genetic variants on structure Together, this comprehensive analysis contributes insights into enhances our understanding regulation function general.

Язык: Английский

Процитировано

7
An atlas of chromatin landscape in KSHV-infected cells during de novo infection and reactivation DOI Creative Commons
Tomoki Inagaki, Ashish Kumar,

Somayeh Komaki

и другие.

Virology, Год журнала: 2024, Номер 597, С. 110146 - 110146

Опубликована: Июнь 19, 2024

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus with a double-stranded DNA capable of establishing latent infection in the host cell. During latency, only limited number viral genes are expressed infected cells, and that helps virus to evade immune cell response. primary infection, KSHV genome chromatinized maintained as episome, which tethered chromosome via Latency Associated Nuclear Antigen (LANA). The episome undergoes same chromatin modification and, therefore, regulated by various epigenetic modifications, such methylation, histone acetylation. also organized spatiotemporal manner forming genomic loops, enable simultaneous coordinated control dynamic gene transcription, particularly during lytic replication phase. genome-wide approaches advancing bioinformatic tools have increased resolution studies on transcriptional our understanding latency-lytic switch regulation. We will summarize current regulation chromatin.

Язык: Английский

Процитировано

5
Spatial promoter–enhancer hubs in cancer: organization, regulation, and function DOI Creative Commons
Jingru Zhao, Robert B. Faryabi

Trends in cancer, Год журнала: 2023, Номер 9(12), С. 1069 - 1084

Опубликована: Авг. 19, 2023

Язык: Английский

Процитировано

13
Transcription Factor Condensates Mediate Clustering ofMETRegulon and Enhancement in Gene Expression DOI Creative Commons
James Lee,

Leman Simpson,

Yi Li

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 8, 2024

Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3D genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast Met4 a few co-activators, including Met32, induce set genes involved met biosynthesis. Here, we show that endogenous Met32 co-localized puncta-like structures nuclei upon depletion. Recombinant mixed droplets with LLPS properties vitro . relation chromatin, puncta co-localize target genes, at least subset are clustered Met4-dependent manner. A MET3pr -GFP reporter inserted near several native binding sites becomes displays enhanced transcriptional activity. variant partial truncation an intrinsically disordered region (IDR) shows less formation, this mutant selectively reduces activity basal level. Overall, results support model where co-activators bring multiple into vicinity higher local concentrations, which facilitates strong

Язык: Английский

Процитировано

4
Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon DOI Creative Commons
James Lee,

Leman Simpson,

Yi Li

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Май 2, 2024

Some transcription factors (TFs) can form liquid–liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3-Dimentional (3D) genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast Met4 a few co-activators, including Met32, induce set genes involved met biosynthesis. Here, we show that endogenous Met32 co-localized puncta-like structures nuclei upon depletion. Recombinant mixed droplets with LLPS properties vitro. relation chromatin, puncta co-localize target genes, at least subset is clustered 3D Met4-dependent manner. A MET3pr -GFP reporter inserted near several native Met4-binding sites becomes displays enhanced transcriptional activity. variant partial truncation an intrinsically disordered region (IDR) shows less formation, this mutant selectively reduces activity basal level. Overall, results support model where co-activators bring multiple into vicinity higher local concentrations, which facilitates strong

Язык: Английский

Процитировано

4
TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene DOI Creative Commons
Evelyn Kabirova, Anastasia I. Ryzhkova, Varvara Lukyanchikova

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 28, 2024

Abstract Topologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements TADs boundaries do not always lead to significant changes in activity pattern. Here, we investigated consequences TAD deletion on expression developmentally important genes encoding tyrosine kinase receptors: Kit, Kdr, Pdgfra . We used genome editing mice delete at Kit locus and characterized chromatin folding pure cultures fibroblasts, mast cells, melanocytes. found that although is highly active both cells melanocytes, boundary between Kdr results ectopic activation only Thus, epigenetic landscape, namely mutual arrangement enhancers actively transcribing genes, for predicting removal. also without a border have phenotypic manifestation mutation — lighter coloration. data obtained shed light principles interaction 3D organization marks regulation

Язык: Английский

Процитировано

4
CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant DOI Creative Commons
Samuel J. Kaplan, Wilfred Wong, Jielin Yan

и другие.

Cell Reports, Год журнала: 2024, Номер 43(8), С. 114640 - 114640

Опубликована: Авг. 1, 2024

Functional enhancer annotation is critical for understanding tissue-specific transcriptional regulation and prioritizing disease-associated non-coding variants. However, unbiased discovery in disease-relevant contexts remains challenging. To identify enhancers pertinent to diabetes, we conducted a CRISPR interference (CRISPRi) screen the human pluripotent stem cell (hPSC) pancreatic differentiation system. Among identified, focused on an named ONECUT1e-664kb, ∼664 kb from ONECUT1 promoter. Previous studies have linked coding mutations hypoplasia neonatal diabetes. We found that homozygous deletion of ONECUT1e-664kb hPSCs leads near-complete loss expression impaired differentiation. contains type 2 diabetes-associated variant (rs528350911) disrupting GATA motif. Introducing risk into reduced binding key transcription factors (GATA4, GATA6, FOXA2), supporting its causal role This work highlights utility settings monogenic complex disease.

Язык: Английский

Процитировано

4
Transcription factor condensates, 3D clustering, and gene expression enhancement of the MET regulon DOI Creative Commons

James Lee,

Leman Simpson,

Yi Li

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Сен. 30, 2024

Some transcription factors (TFs) can form liquid–liquid phase separated (LLPS) condensates. However, the functions of these TF condensates in 3-Dimentional (3D) genome organization and gene regulation remain elusive. In response to methionine (met) starvation, budding yeast Met4 a few co-activators, including Met32, induce set genes involved met biosynthesis. Here, we show that endogenous Met32 co-localized puncta-like structures nuclei upon depletion. Recombinant mixed droplets with LLPS properties vitro. relation chromatin, puncta co-localize target genes, at least subset is clustered 3D Met4-dependent manner. A MET3pr -GFP reporter inserted near several native Met4-binding sites becomes displays enhanced transcriptional activity. variant partial truncation an intrinsically disordered region (IDR) shows less formation, this mutant selectively reduces activity basal level. Overall, results support model where co-activators bring multiple into vicinity higher local concentrations, which facilitates strong

Язык: Английский

Процитировано

4