生物大分子“液–液相分离”调控染色质三维空间结构和功能

生物大分子的相分离聚集(简称相分离)是驱动细胞内无膜细胞器形成的主要机制,参与众多生物学过程并和多种人类疾病密切相关,如神经退行性疾病等。近年来,研究人员围绕相分离现象的分子机制和生物学功能,发现了相分离与信号传导、染色质结构、基因表达、转录调控等一系列生物学过程存在紧密关联,为理解细胞命运决定和疾病发生提供了新的视角,为疾病治疗和新药研发开辟了新的可能途径。本文在回顾了相分离研究的发展过程、相分离现象在生物学中的应用,以及相分离与疾病的关系的基础上,重点分析了近年来相分离与染色质结构关联方面的研究突破,包括相分离如何感知并重塑染色质结构、超级增强子如何通过相分离调节基因表达、共转录激活因子如何通过相分离参与基因表达调控等,以期为进一步理解相分离与染色质空间结构的关系提供参考。

Micro or nano:Evaluation of biosafety and biopotency of magnesium metal organic framework-74 with different particle sizes

In recent years,various particulate materials have played important roles in medical applications.However,nano-and micron-sized particles of the same material could exhibit distinct properties due to different particle sizes.This finding provided a simple and effective way to improve the biological applications of particulate materials.Therefore,as a highly promising member,the effect of the particle size change of the magnesium metal organic framework-74(Mg-MOF74)was well worth evaluating.Here we firsth assessed the in vitro and in vivo toxicity of micron/nanoscale Mg-MOF74(m-Mg-MOF74/n-Mg-MOF74)in detail.Our in vitro study revealed that compared to micron-sized subjects,n-Mg-MOF74 provided a wider range of safe concentrations.Furthermore,both micron/nanoscale Mg-MOF74 showed good biocompatibility and allowed all the rats under the treatment to survive through the expected experimental periods,with n-Mg-MOF74 still showing lower cardiotoxicity.These advantages of nanoscale Mg-MOF74might benefit from its sustainable and balanced release of Ma^2+both inside and outside the cells.Based on the biosafety evaluation,advanced bio-functional assessments of m/n-Mg-MOF74 including early osteogenesis and angiogenesis were alsoperformed.Similarly,the suitable dose groups of n-Mg-MOF74 achieved optimal early osteogenic promotion and angiogenic stimulation effects.Overall,our combined data delineated the toxicity and biological behaviors of Ma-MOF74 of different scales,and sugqested nanoscale Mg-MOF74 as a better choice for future applications.This result revealed that particle size reductior might be a viable strategy to improve and expand medical applications of MOFs or other particulate materials.

WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit

The dysregulation of transcription factors is widely associated with tumorigenesis.As the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstream genes.Given that there is no effective way to directly inhibit c-Myc,c-Myc targeting strategies hold great potential for cancer therapy.In this study,we found that WSB1,which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples,is a direct target gene of c-Myc,and can positively regulate c-Myc expression,which forms a feedforward circuit promoting cancer development.RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted cMyc expression through theβ-catenin pathway.Mechanistically,WSB1 affectedβ-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptorβ-TRCP recruitment,which inhibited the ubiquitination ofβ-catenin and transactivated c-Myc.Of interest,the effect of WSB1 on c-Myc was independent of its E3 ligase activity.Moreover,overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression.Thus,our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role,highlighting a potential c-Myc intervention strategy in cancer treatment.