Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis DOI Creative Commons
Jinmei Cheng, Yi‐Min Gu,

Yueming Wang

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(3)

Published: Jan. 24, 2025

Abstract Chromatin remodeling, which involves the histone-to-protamine exchange process during spermiogenesis, is crucial for sperm nuclear condensation and male fertility. However, key regulators underlying molecular mechanisms involved in this remain largely unexplored. In study, we discovered that deficiency family with sequence similarity 170 member A (Fam170a) led to abnormal morphology infertility mice, mirroring observation of very low Fam170a transcription levels infertile men teratozoospermia. Further investigation revealed plays a significant role chromatin remodeling process. This was evidenced by earlier core histone removal, accelerated translation degradation transition proteins, reduced protamine incorporation spermiogenesis Fam170a-deleted mice. Mechanistically, found interacts remodeling-associated proteins regulates genes related remodeling. Notably, directly deubiquitinating enzyme Usp7 facilitates its translocation elongating sperm, enhancing activity on testis-specific H2A H2B variants. Collectively, our findings identify as previously unrecognized regulator suggest deubiquitination may play an essential

Language: Английский

Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome DOI Creative Commons
Jiangbo Lu, Lei Chang, Tong Li

et al.

Cell Research, Journal Year: 2021, Volume and Issue: 31(6), P. 613 - 630

Published: Jan. 29, 2021

Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved relatively stable during lineage differentiation. In an effort unravel basic principle underlying folding, here we focus on itself report a fundamental role for L1 (LINE1 or LINE-1) B1/Alu retrotransposons, most abundant subclasses repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering demarcates grossly exclusive domains, characterizes predicts Hi-C compartments. Spatial segregation L1-rich sequences nuclear nucleolar peripheries B1/Alu-rich interior is mouse human cells occurs dynamically cell cycle. addition, de novo establishment B1 coincident with formation higher-order structures early embryogenesis critically regulated by transcripts. Importantly, depletion transcripts embryonic stem drastically weakens repeat contacts compartmental strength, disrupts L1- B1-rich chromosomal at genome-wide individual sites. Mechanistically, co-localization liquid droplet DNA RNA protein HP1α suggest phase-separation mechanism which promotes Taken together, propose genetically encoded model repeats blueprint macrostructure. Our explains robustness folding common core, dynamic gene regulation overlaid across cells.

Language: Английский

Citations

163
Lamina-associated domains: Tethers and looseners DOI
Stefano Giustino Manzo, Lise Dauban, Bas van Steensel

et al.

Current Opinion in Cell Biology, Journal Year: 2022, Volume and Issue: 74, P. 80 - 87

Published: Feb. 1, 2022

Language: Английский

Citations

55
Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging DOI Creative Commons
Zunpeng Liu, Qianzhao Ji, Jie Ren

et al.

Developmental Cell, Journal Year: 2022, Volume and Issue: 57(11), P. 1347 - 1368.e12

Published: May 24, 2022

Language: Английский

Citations

55
Gene architecture directs splicing outcome in separate nuclear spatial regions DOI Creative Commons
Luna Tammer, Ofir Hameiri, Ifat Keydar

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(5), P. 1021 - 1034.e8

Published: Feb. 18, 2022

Language: Английский

Citations

52
XIST loss impairs mammary stem cell differentiation and increases tumorigenicity through Mediator hyperactivation DOI Creative Commons
Laia Richart,

Mary-Loup Picod-Chedotel,

Michel Wassef

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2164 - 2183.e25

Published: May 20, 2022

Language: Английский

Citations

47
Compartmentalization with nuclear landmarks yields random, yet precise, genome organization DOI Creative Commons
Kartik Kamat,

Zhuohan Lao,

Yifeng Qi

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(7), P. 1376 - 1389

Published: March 5, 2023

Language: Английский

Citations

29
Chromosome compartmentalization: causes, changes, consequences, and conundrums DOI
Heng Li, Christopher Playter, Priyojit Das

et al.

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 707 - 727

Published: Feb. 22, 2024

Language: Английский

Citations

14
Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism DOI Creative Commons
Emily M. Pujadas-Liwag,

Xiaolong Wei,

Nicolas Acosta

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 22, 2024

B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous using Auxin-inducible degron technology.

Language: Английский

Citations

14
Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation DOI

Jagdish Mishra,

Subhajit Chakraborty,

Niharika Niharika

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 12, 2024

Abstract Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in cell's physical surroundings. These of impose mechanical tension intracellular protein network (both cytosolic nuclear). could released by series protein–protein interactions often facilitated membrane lipids, lectins sugar molecules thus generate type signal drive cellular processes, including differentiation, polarity, growth, adhesion, movement, survival. Recent experimental data have accentuated molecular mechanism this transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins plasma discern channel information interior. Cells respond message altering their arrangement directly transmitting nucleus through connection cytoskeleton nucleoskeleton before despatched biochemical signaling pathways. Nuclear transmission force leads activation chromatin modifiers modulation epigenetic landscape, inducing reorganization gene expression regulation; time chemical messengers (transcription factors) arrive into nucleus. While significant research has been done on role mechanotransduction tumor development cancer progression/metastasis, mechanistic basis force‐activated carcinogenesis is still enigmatic. Here, review, we discussed various cues connections better comprehend also explored detailed some multiple players (proteins macromolecular complexes) involved Thus, described an avenue: how stress directs modulate epigenome cells aberrant phenotype.

Language: Английский

Citations

10
Regulation of Nuclear Mechanics and the Impact on DNA Damage DOI Open Access
Ália dos Santos, Christopher P. Toseland

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(6), P. 3178 - 3178

Published: March 20, 2021

In eukaryotic cells, the nucleus houses genomic material of cell. The physical properties and its ability to sense external mechanical cues are tightly linked regulation cellular events, such as gene expression. Nuclear mechanics morphology altered in many diseases cancer premature ageing syndromes. Therefore, it is important understand how different components contribute nuclear processes, organisation mechanics, they misregulated disease. Although, over years, studies have focused on lamina—a mesh intermediate filament proteins residing between chromatin membrane—there growing evidence that structure factors regulate essential contributors nucleus. Here, we review main structural nucleus, with particular emphasis structure. We also provide an example stiffness can both impact be affected by processes DNA damage repair.

Language: Английский

Citations

43