Chromosome structure in Drosophila is determined by boundary pairing not loop extrusion

eLife, Год журнала: 2024, Номер 13

Опубликована: Фев. 5, 2024

Two different models have been proposed to explain how the endpoints of chromatin looped domains (‘TADs’) in eukaryotic chromosomes are determined. In first, a cohesin complex extrudes loop until it encounters boundary element roadblock, generating stem-loop. this model, boundaries functionally autonomous: they an intrinsic ability halt movement incoming complexes that is independent properties neighboring boundaries. second, loops generated by boundary:boundary pairing. non-autonomous, and their form depends upon well match with neighbors. Moreover, unlike loop-extrusion pairing interactions can generate both stem-loops circle-loops. We used combination MicroC analyze TADs organized, experimental manipulations even skipped TAD boundary, homie , test predictions ‘loop-extrusion’ ‘boundary-pairing’ models. Our findings incompatible instead suggest flies determined mechanism which elements physically pair partners, either head-to-head or head-to-tail, varying degrees specificity. Although our experiments do not address partners find each other, unlikely require extrusion.

Язык: Английский

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C2H2-zinc-finger transcription factors bind RNA and function in diverse post-transcriptional regulatory processes

Molecular Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Zinc finger protein transcription factors: Integrated line of action for plant antimicrobial activity

Microbial Pathogenesis, Год журнала: 2019, Номер 132, С. 141 - 149

Опубликована: Апрель 30, 2019

Язык: Английский

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Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status

Epigenetics, Год журнала: 2019, Номер 14(8), С. 751 - 765

Опубликована: Май 7, 2019

This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in placenta. SES was defined by presence of, as well a summative count four factors: less than college education, single marital status, food and nutritional service assistance, public health insurance. Epigenome-wide assessed using Illumina EPIC array 426 placentas from sample of infants born < 28 weeks gestation Extremely Low Gestational Age Newborn cohort. Associations between were robust linear regressions adjusted for covariates controlled false discovery rate at 10%. We also examined whether such associations sex specific. Indicators differential 33 CpG sites. Of identified sites, 19 (57.6%) displayed increased methylation, 14 (42.4%) decreased association least one factors. Sex differences observed score; which derived female pregnancies showed more male pregnancies. Maternal genes key role gene transcription placental function, potentially altering immunity stress response. Further investigation needed to evaluate epigenetic mediating during pregnancy later life outcomes children.

Язык: Английский

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ZNF677 Suppresses Akt Phosphorylation and Tumorigenesis in Thyroid Cancer

Cancer Research, Год журнала: 2018, Номер 78(18), С. 5216 - 5228

Опубликована: Июль 11, 2018

The zinc finger protein 677 (ZNF677) belongs to the family, which possesses transcription factor activity by binding sequence-specific DNA. Previous studies have reported its downregulated promoter methylation in non-small cell lung cancer. However, biological role and exact mechanism human cancers, including thyroid cancer, remain unknown. In this study, we demonstrate that ZNF677 is frequently primary papillary cancers (PTC) show decreased expression of significantly associated with poor patient survival. Ectopic cancer cells dramatically inhibited proliferation, colony formation, migration, invasion, tumorigenic potential nude mice induced cell-cycle arrest apoptosis. Conversely, knockdown promoted proliferation formation. exerted tumor suppressor functions through transcriptional repression two targets CDKN3 HSPB1 (or HSP27), thereby inhibiting phosphorylation activation Akt via distinct mechanisms. Taken together, our data as a silenced cancer.Significance: These findings report suppressive zinc-finger inhibition phosphorylation. Cancer Res; 78(18); 5216-28. ©2018 AACR.

Язык: Английский

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Structural zinc binding sites shaped for greater works: Structure-function relations in classical zinc finger, hook and clasp domains

Journal of Inorganic Biochemistry, Год журнала: 2019, Номер 204, С. 110955 - 110955

Опубликована: Дек. 5, 2019

Metal ions are essential elements present in biological systems able to facilitate many cellular processes including proliferation, signaling, DNA synthesis and repair. Zinc ion (Zn(II)) is an important cofactor for numerous biochemical reactions. Commonly, structural zinc sites demonstrate high Zn(II) affinity compact architecture required sequence-specific macromolecule binding. However, how Zn(II)-dependent proteins fold, their dissociation occurs, which factors modulate protein as well stability remains not fully understood. The molecular rules governing precise regulation of function hidden the relationship between sequence structure, hence require deep understanding folding mechanism under metal load, reactivity metal-to-protein affinity. Even though, this sequence-structure has impact on function, it been shown that other localization availability influence overall behavior. Taking into account all mentioned factors, review, we aim describe structure-function-stability sites, found a finger, hook clasps, reach far beyond point view order appreciate balance chemistry biology govern world.

Язык: Английский

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Molecular mechanisms of topoisomerase 2 DNA–protein crosslink resolution

Cellular and Molecular Life Sciences, Год журнала: 2019, Номер 77(1), С. 81 - 91

Опубликована: Ноя. 15, 2019

Язык: Английский

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Mechanisms of Enhancer-Promoter Interactions in Higher Eukaryotes

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(2), С. 671 - 671

Опубликована: Янв. 12, 2021

In higher eukaryotes, enhancers determine the activation of developmental gene transcription in specific cell types and stages embryogenesis. Enhancers transform signals produced by various factors within a given cell, activating targeted genes. Often, genes can be associated with dozens enhancers, some which are located at large distances from promoters that they regulate. Currently, mechanisms underlying distance interactions between remain poorly understood. This review briefly describes properties discusses potential proteins involved this process.

Язык: Английский

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Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Авг. 16, 2024

Abstract Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, inadequate analysis variants as well larger mutations, such small insertions/deletions (indels) structural (SVs). Method In this study, we performed whole genome sequencing (WGS) conducted single nucleotide (SNVs), indels, SVs, cohort 1,718 cases 2,944 controls European ancestry. Of individuals, 1,441 autopsy-confirmed 277 clinically diagnosed. Results Our common SNVs indels confirmed known genetic loci at MAPT , MOBP S TX6 SLCO1A2 DUSP10 SP1 further uncovered novel signals APOE FCHO1/MAP1S, KIF13A, TRIM24, TNXB, ELOVL1 . Notably, contrast to Alzheimer’s (AD), observed ε2 allele be risk PSP. Analysis identified significant ZNF592 gene network module neuronal genes dysregulated Moreover, seven SVs associated with H1/H2 haplotype region (17q21.31) other loci, including IGH PCMT1 CYP2A13 SMCP region, there burden deletions duplications ( P = 6.73 × 10 –3 ) Conclusions Through WGS, significantly enhanced our understanding basis PSP, providing new targets exploring mechanisms therapeutic interventions.

Язык: Английский

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C2H2 proteins: Evolutionary aspects of domain architecture and diversification

BioEssays, Год журнала: 2024, Номер 46(8)

Опубликована: Июнь 14, 2024

The largest group of transcription factors in higher eukaryotes are C2H2 proteins, which contain C2H2-type zinc finger domains that specifically bind to DNA. Few well-studied however, demonstrate their key role the control gene expression and chromosome architecture. Here we review features domain architecture proteins likely origin fingers. A comprehensive investigation proteomes for presence with multiple clustered has revealed a difference between groups organisms. Unlike plants, metazoans clusters typically separated by linker TGEKP consensus sequence. average size varies substantially, even genomes metazoans, tendency increase combination SCAN, especially KRAB domains, reflecting increasing complexity regulatory networks.

Язык: Английский

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