Functional specialization of Aurora kinase homologs during oogenic meiosis in the tunicate Oikopleura dioica DOI Creative Commons
Haiyang Feng, Eric M. Thompson

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 7, 2023

A single Aurora kinase found in non-vertebrate deuterostomes is assumed to represent the ancestor of vertebrate Auroras A/B/C. However, tunicate Oikopleura dioica , a member sister group vertebrates, possesses two kinases (Aurora1 and Aurora2) that are expressed proliferative cells reproductive organs. Previously, we have shown relocate from organizing centers meiotic nuclei were enriched on centromeric regions as meiosis proceeds metaphase I. Here, assessed their respective functions oogenic using dsRNA interferences. We Aurora1 (Aur1) was involved spindle organization chromosome congression, probably through regulation microtubule dynamics, whereas Aurora2 (Aur2) crucial for condensation assembly. In vitro assays showed Aur1 Aur2 had comparable levels activities. Using yeast two-hybrid library screening, identified few novel interaction proteins Aur1, including c-Jun-amino-terminal kinase-interacting protein 4, cohesin loader Scc2, mitochondrial carrier homolog 2, suggesting may an altered network participate motors complexes O. .

Language: Английский

Enhancer–promoter contact formation requires RNAPII and antagonizes loop extrusion DOI
Shu Zhang, Nadine Übelmesser,

Mariano Barbieri

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(5), P. 832 - 840

Published: April 3, 2023

Language: Английский

Citations

110
Looping the Genome with SMC Complexes DOI Creative Commons
Eugene Kim, Roman Barth, Cees Dekker

et al.

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 15 - 41

Published: May 3, 2023

SMC (structural maintenance of chromosomes) protein complexes are an evolutionarily conserved family motor proteins that hold sister chromatids together and fold genomes throughout the cell cycle by DNA loop extrusion. These play a key role in variety functions packaging regulation chromosomes, they have been intensely studied recent years. Despite their importance, detailed molecular mechanism for extrusion remains unresolved. Here, we describe roles SMCs chromosome biology particularly review vitro single-molecule studies recently advanced our understanding proteins. We mechanistic biophysical aspects govern genome organization its consequences.

Language: Английский

Citations

56
NIPBL and cohesin: new take on a classic tale DOI Creative Commons
Dácil Alonso Gil, Ana Losada

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(10), P. 860 - 871

Published: April 15, 2023

Cohesin folds the genome in dynamic chromatin loops and holds sister chromatids together. NIPBLScc2 is currently considered cohesin loader, a role that may need reevaluation. NIPBL activates ATPase, which required for topological entrapment of DNAs to fuel DNA loop extrusion, but not association. Mechanistic dissection these processes suggests both STAG subunit bind DNA. also regulates conformational switches complex. Interactions with factors, including remodelers, replication proteins, transcriptional machinery, affect loading distribution. Here, we discuss recent research addressing how modulates activities its mutation causes developmental disorder, Cornelia de Lange Syndrome (CdLS).

Language: Английский

Citations

28
Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2 DOI Creative Commons
Dácil Alonso Gil, Ana Cuadrado, Daniel Giménez-Llorente

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 10, 2023

Cohesin organizes the genome through formation of chromatin loops. NIPBL activates cohesin's ATPase and is essential for loop extrusion, but its requirement cohesin loading unclear. Here we have examined effect reducing levels on behavior two variants carrying STAG1 or STAG2 by combining a flow cytometry assay to measure chromatin-bound with analyses genome-wide distribution contacts. We show that depletion results in increased cohesin-STAG1 further accumulates at CTCF positions while cohesin-STAG2 diminishes genome-wide. Our data are consistent model which may not be required association it turn facilitates stabilization after being loaded elsewhere. In contrast, binds becomes stabilized sites even under low levels, folding severely impaired.

Language: Английский

Citations

23
An extrinsic motor directs chromatin loop formation by cohesin DOI Creative Commons
Thomas M Guérin, Christopher Barrington, Georgii Pobegalov

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(19), P. 4173 - 4196

Published: Aug. 19, 2024

Language: Английский

Citations

9
A replication fork determinant for the establishment of sister chromatid cohesion DOI Creative Commons
Masashi Minamino, Céline Bouchoux, Berta Canal

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 837 - 849.e11

Published: Jan. 23, 2023

Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Cohesion establishment requires acetylation of conserved lysine residues by Eco1 acetyltransferase. Here, we explore how is linked to replication. Biochemical reconstitution replication-coupled reveals that transient structures, which form during control reaction. As polymerases complete lagging strand displacement synthesis produces flaps are trimmed result in nicked double-stranded DNA. Both and nicks stimulate acetylation, while subsequent nick ligation Okazaki fragment maturation terminates A flapped or substrate constitutes a molecular clue directs window behind replication fork, next where likely entraps both Our results provide an explanation for chromatid establishment.

Language: Английский

Citations

22
Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion DOI Creative Commons
Shu Zhang, Nadine Übelmesser,

Mariano Barbieri

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 4, 2022

SUMMARY Mammalian chromosomes are folded by converging and opposing forces. Here, we tested the role of RNAPII across different scales interphase chromatin folding in a cellular system allowing for its auxin-mediated degradation. We used Micro-C computational modeling to characterize subsets loops differentially gained or lost upon depletion. Gained loops, extrusion which was antagonized RNAPII, almost invariably formed engaging new rewired CTCF anchors. Lost selectively concerned contacts between enhancers promoters anchored RNAPII. Surprisingly, promoter-promoter were insensitive polymerase depletion sustained cohesin occupancy absence. Selective loss enhancer-promoter explains repression most genes. Together, our findings reconcile transcription with that setting-up regulatory 3D architectures genome-wide, while also revealing direct impact on loop extrusion.

Language: Английский

Citations

19
Liquid condensates: a new barrier to loop extrusion? DOI Creative Commons

Arseniy V. Selivanovskiy,

Maria N. Molodova,

Ekaterina E. Khrameeva

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Feb. 20, 2025

Liquid–liquid phase separation (LLPS), driven by dynamic, low-affinity multivalent interactions of proteins and RNA, results in the formation macromolecular condensates on chromatin. These structures are likely to provide high local concentrations effector factors responsible for various processes including transcriptional regulation DNA repair. In particular, enhancers, super-enhancers, promoters serve as platforms condensate assembly. current paradigm, enhancer-promoter (EP) interaction could be interpreted a result enhancer- promoter-based contact/fusion. There is increasing evidence that spatial juxtaposition enhancers provided loop extrusion (LE) SMC complexes. Here, we propose may act barriers LE, thereby contributing nuclear contacts between regulatory genomic elements.

Language: Английский

Citations

0
Cohesin mediated loop extrusion from active enhancers form chromatin jets inC. elegans DOI Creative Commons
Jun Kim, Haoyu Wang, Sevinç Ercan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 20, 2023

In mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between

Language: Английский

Citations

10
Mediator complex in transcription regulation and DNA repair: Relevance for human diseases DOI Creative Commons

Christelle A. Maalouf,

Adriana Alberti, Julie Soutourina

et al.

DNA repair, Journal Year: 2024, Volume and Issue: 141, P. 103714 - 103714

Published: June 24, 2024

The Mediator complex is an essential coregulator of RNA polymerase II transcription. More recent developments suggest functions as a link between transcription regulation, genome organisation and DNA repair mechanisms including nucleotide excision repair, base homologous recombination. Dysfunctions these processes are frequently associated with human pathologies, growing evidence shows involvement in cancers, neurological, metabolic infectious diseases. detailed deciphering molecular functions, using interdisciplinary approaches different biological models considering all this complex, will contribute to our understanding relevant

Language: Английский

Citations

3