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1.
Cell Regen ; 11(1): 25, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35915272

RESUMO

Mouse embryonic stem cells (mESCs) cycle in and out of a transient 2-cell (2C)-like totipotent state, driven by a complex genetic circuit involves both the coding and repetitive sections of the genome. While a vast array of regulators, including the multi-functional protein Rif1, has been reported to influence the switch of fate potential, how they act in concert to achieve this cellular plasticity remains elusive. Here, by modularizing the known totipotency regulatory factors, we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repressive complex PRC1.6. Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs. The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6, bolstering the intactness of the PRC1.6 complex. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state. Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352, but also derepresses a group of the endogenous retroviral element MERVL, a key marker for totipotency. Collectively, our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential, shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.

2.
Nat Commun ; 13(1): 3501, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715442

RESUMO

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription.


Assuntos
Retrovirus Endógenos , Fatores de Transcrição , Proteínas de Ciclo Celular/genética , Cromatina/genética , Elementos de DNA Transponíveis , Proteínas de Ligação a DNA/genética , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética
3.
Phys Chem Chem Phys ; 17(38): 25182-90, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26352766

RESUMO

Ag/AgCl-based plasmonic photocatalysts have received much attention as emerging visible-light-driven photocatalysts, wherein those characterized by 1D morphology have aroused great expectations. Most of the current existing protocols for the fabrication of 1D materials, however, suffer from either multistep tedious synthesis processes or the requirement of rigorous experimental conditions. A one-pot fabrication method feasible under ambient conditions is strongly desired. By means of a surfactant-assisted protocol, we report herein that Ag/AgCl structures of near-spherical and 1D morphology could be controllably produced. We show that near-spherical Ag/AgCl species could be produced immediately after dropping an AgNO3 aqueous solution into an aqueous solution of cetyltrimethylammonium chloride (CTAC) surfactant under stirring. Interestingly, we show that these initially formed near-spherical species could automatically evolve into 1D Ag/AgCl fibers simply by extending the stirring time under ambient conditions. In our new protocol, CTAC works not only as a chlorine source but also as a directing reagent to assist the formation of 1D Ag/AgCl structures. Moreover, we demonstrate that compared to near-spherical structures, our Ag/AgCl fibers could display boosted catalytic performances towards the photodegradation of the methyl orange pollutant under visible light irradiation. Our work might launch an easy method for the construction of fibrous Ag/AgCl architectures of superior photocatalytic reactivity, and it also provides deep insights into the surfactant-assisted synthesis.

4.
Langmuir ; 31(1): 602-10, 2015 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-25487042

RESUMO

We herein report that spherical and sheetlike Ag/AgCl nanostructures could be controllably synthesized by means of chemical reactions between AgNO3 and cetyltrimethylammonium chloride (CTAC) surfactant. In this synthesis system, AgNO3 works as the silver source, while CTAC serves not only as the chlorine source but also as the directing reagent for a controllable nanofabrication. We show that compared to the spherical Ag/AgCl nanostructures, the sheetlike counterparts, wherein the AgCl nanospecies are predominantly enriched with {111} facets, could exhibit superior catalytic performances toward the photodegradation of methyl orange. Interestingly, we further demonstrate that when 4-chlorophenol or phenol is used as the substrate, the sheetlike Ag/AgCl nanostructures exhibit inferior catalytic reactivity, whereas the spherical counterparts display superior catalytic performances comparatively. Our results disclose new insights on the facet-dependent catalytic performances with regard to a facet-selective but substrate-sensitive photoinduced electron-hole separation.

5.
Sci Rep ; 4: 5259, 2014 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-24918973

RESUMO

Well-defined noble metal nanocrystals (NMNCs) of a unique morphology yet a uniform facet have attracted broad interests. In this regard, those with a highly branched architecture have gained particular attention. Most of the currently existing branched NMNCs, however, are enclosed by mixed facets. We now report that branched Au nanoarchitectures could be facilely fabricated by mixing an aqueous solution of KAuCl4, an aqueous dispersion of graphene oxide, and ethanol under ambient conditions. Interestingly, unilike the conventional branched NMNCs, our unique Au nanostructures are predominately enriched with a uniform facet of {111}. Compared to the spherical Au nanostructures exposed with mixed facets, our branched nanospecies of a uniform facet display superior catalytic performances both for the catalytic reduction of 4-nitrophenol and the electrocatalytic oxidation of methanol. Our investigation represents the first example that Au nanostructures simultaneously featured with a highly branched architecture and a uniform crystal facet could be formulated. Our unique Au nanostructures provide a fundamental yet new scientific forum to disclose the correlation between the surface atomic arrangement and the catalytic performances of branched NMNCs.

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