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

Yueming Wang

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(3)

Опубликована: Янв. 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

Язык: Английский

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

и другие.

Cell Research, Год журнала: 2021, Номер 31(6), С. 613 - 630

Опубликована: Янв. 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.

Язык: Английский

Процитировано

163

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

и другие.

Current Opinion in Cell Biology, Год журнала: 2022, Номер 74, С. 80 - 87

Опубликована: Фев. 1, 2022

Язык: Английский

Процитировано

55

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

и другие.

Developmental Cell, Год журнала: 2022, Номер 57(11), С. 1347 - 1368.e12

Опубликована: Май 24, 2022

Язык: Английский

Процитировано

55

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

и другие.

Molecular Cell, Год журнала: 2022, Номер 82(5), С. 1021 - 1034.e8

Опубликована: Фев. 18, 2022

Язык: Английский

Процитировано

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

и другие.

Cell, Год журнала: 2022, Номер 185(12), С. 2164 - 2183.e25

Опубликована: Май 20, 2022

Язык: Английский

Процитировано

47

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

Zhuohan Lao,

Yifeng Qi

и другие.

Biophysical Journal, Год журнала: 2023, Номер 122(7), С. 1376 - 1389

Опубликована: Март 5, 2023

Язык: Английский

Процитировано

29

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

и другие.

Trends in Cell Biology, Год журнала: 2024, Номер 34(9), С. 707 - 727

Опубликована: Фев. 22, 2024

Язык: Английский

Процитировано

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

и другие.

Genome biology, Год журнала: 2024, Номер 25(1)

Опубликована: Март 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.

Язык: Английский

Процитировано

14

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

Jagdish Mishra,

Subhajit Chakraborty,

Niharika Niharika

и другие.

Journal of Cellular Biochemistry, Год журнала: 2024, Номер 125(3)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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, Год журнала: 2021, Номер 22(6), С. 3178 - 3178

Опубликована: Март 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.

Язык: Английский

Процитировано

43