Molecular Cell最新文献_第6页

Live-cell imaging of RNA Pol II and elongation factors distinguishes competing mechanisms of transcription regulation RNA Pol II 和延伸因子的活细胞成像可区分相互竞争的转录调控机制

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-08 DOI: 10.1016/j.molcel.2024.07.009

{"title":"Live-cell imaging of RNA Pol II and elongation factors distinguishes competing mechanisms of transcription regulation","authors":"","doi":"10.1016/j.molcel.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.009","url":null,"abstract":"RNA polymerase II (RNA Pol II)-mediated transcription is a critical, highly regulated process aided by protein complexes at distinct steps. Here, to investigate RNA Pol II and transcription-factor-binding and dissociation dynamics, we generated endogenous photoactivatable-GFP (PA-GFP) and HaloTag knockins using CRISPR-Cas9, allowing us to track a population of molecules at the induced Hsp70 loci in Drosophila melanogaster polytene chromosomes. We found that early in the heat-shock response, little RNA Pol II and DRB sensitivity-inducing factor (DSIF) are reused for iterative rounds of transcription. Surprisingly, although PAF1 and Spt6 are found throughout the gene body by chromatin immunoprecipitation (ChIP) assays, they show markedly different binding behaviors. Additionally, we found that PAF1 and Spt6 are only recruited after positive transcription elongation factor (P-TEFb)-mediated phosphorylation and RNA Pol II promoter-proximal pause escape. Finally, we observed that PAF1 may be expendable for transcription of highly expressed genes where nucleosome density is low. Thus, our live-cell imaging data provide key constraints to mechanistic models of transcription regulation.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FACT mediates the depletion of macroH2A1.2 to expedite gene transcription FACT 介导宏观 H2A1.2 的消耗，以加速基因转录

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-07 DOI: 10.1016/j.molcel.2024.07.011

{"title":"FACT mediates the depletion of macroH2A1.2 to expedite gene transcription","authors":"","doi":"10.1016/j.molcel.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.011","url":null,"abstract":"The histone variant macroH2A is generally linked to transcriptionally inactive chromatin, but how macroH2A regulates chromatin structure and functions in the transcriptional process remains elusive. This study reveals that while the integration of human macroH2A1.2 into nucleosomes does not affect their stability or folding dynamics, it notably hinders the maintenance of facilitates chromatin transcription’s (FACT’s) function. We show that FACT effectively diminishes the stability of macroH2A1.2-nucleosomes and expedites their depletion subsequent to the initial unfolding process. Furthermore, we identify the residue S139 in macroH2A1.2 as a critical switch to modulate FACT’s function in nucleosome maintenance. Genome-wide analyses demonstrate that FACT-mediated depletion of macroH2A-nucleosomes allows the correct localization of macroH2A, while the S139 mutation reshapes macroH2A distribution and influences stimulation-induced transcription and cellular response in macrophages. Our findings provide mechanistic insights into the intricate interplay between macroH2A and FACT at the nucleosome level and elucidate their collective role in transcriptional regulation and immune response of macrophages.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Genome-Wide Analysis Indicates that Yeast Pre-mRNA Splicing Is Predominantly Posttranscriptional 全基因组分析表明酵母前核糖核酸剪接主要是转录后进行的

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-07 DOI: 10.1016/j.molcel.2024.07.031

引用次数: 0

Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation 糖介导的非规范泛素化会损害 Nrf1/NFE2L1 的激活

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-07 DOI: 10.1016/j.molcel.2024.07.013

{"title":"Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation","authors":"","doi":"10.1016/j.molcel.2024.07.013","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.013","url":null,"abstract":"Proteasome is essential for cell survival, and proteasome inhibition induces proteasomal gene transcription via the activated endoplasmic-reticulum-associated transcription factor nuclear factor erythroid 2-like 1 (Nrf1/NFE2L1). Nrf1 activation requires proteolytic cleavage by DDI2 and N-glycan removal by NGLY1. We previously showed that Nrf1 ubiquitination by SKP1-CUL1-F-box (SCF)FBS2/FBXO6, an N-glycan-recognizing E3 ubiquitin ligase, impairs its activation, although the molecular mechanism remained elusive. Here, we show that SCFFBS2 cooperates with the RING-between-RING (RBR)-type E3 ligase ARIH1 to ubiquitinate Nrf1 through oxyester bonds in human cells. Endo-β-N-acetylglucosaminidase (ENGASE) generates asparagine-linked N-acetyl glucosamine (N-GlcNAc) residues from N-glycans, and N-GlcNAc residues on Nrf1 served as acceptor sites for SCFFBS2-ARIH1-mediated ubiquitination. We reconstituted the polyubiquitination of N-GlcNAc and serine/threonine residues on glycopeptides and found that the RBR-specific E2 enzyme UBE2L3 is required for the assembly of atypical ubiquitin chains on Nrf1. The atypical ubiquitin chains inhibited DDI2-mediated activation. The present results identify an unconventional ubiquitination pathway that inhibits Nrf1 activation.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural determinants of DNA cleavage by a CRISPR HNH-Cascade system CRISPR HNH 级联系统切割 DNA 的结构决定因素

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-06 DOI: 10.1016/j.molcel.2024.07.026

引用次数: 0

A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3′ termini 独立于连接的测序方法揭示了 3′末端受阻的 tRNA 衍生 RNA

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-02 DOI: 10.1016/j.molcel.2024.07.008

引用次数: 0

Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance 通过组蛋白去乙酰化排斥核小体重塑者，强化异染色质沉默和表观遗传

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-02 DOI: 10.1016/j.molcel.2024.07.006

{"title":"Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance","authors":"","doi":"10.1016/j.molcel.2024.07.006","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.006","url":null,"abstract":"Heterochromatin enforces transcriptional gene silencing and can be epigenetically inherited, but the underlying mechanisms remain unclear. Here, we show that histone deacetylation, a conserved feature of heterochromatin domains, blocks SWI/SNF subfamily remodelers involved in chromatin unraveling, thereby stabilizing modified nucleosomes that preserve gene silencing. Histone hyperacetylation, resulting from either the loss of histone deacetylase (HDAC) activity or the direct targeting of a histone acetyltransferase to heterochromatin, permits remodeler access, leading to silencing defects. The requirement for HDAC in heterochromatin silencing can be bypassed by impeding SWI/SNF activity. Highlighting the crucial role of remodelers, merely targeting SWI/SNF to heterochromatin, even in cells with functional HDAC, increases nucleosome turnover, causing defective gene silencing and compromised epigenetic inheritance. This study elucidates a fundamental mechanism whereby histone hypoacetylation, maintained by high HDAC levels in heterochromatic regions, ensures stable gene silencing and epigenetic inheritance, providing insights into genome regulatory mechanisms relevant to human diseases.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141880046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering IscB to develop highly efficient miniature editing tools in mammalian cells and embryos 利用 IscB 工程开发哺乳动物细胞和胚胎中的高效微型编辑工具

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-02 DOI: 10.1016/j.molcel.2024.07.007

引用次数: 0

Mrc1 regulates parental histone segregation and heterochromatin inheritance Mrc1调控亲本组蛋白分离和异染色质遗传

IF 16 1区生物学

Molecular Cell Pub Date : 2024-08-01 DOI: 10.1016/j.molcel.2024.07.002

引用次数: 0

The V-ATPase/ATG16L1 axis is controlled by the V1H subunit V-ATPase/ATG16L1 轴由 V1H 亚基控制

IF 16 1区生物学

Molecular Cell Pub Date : 2024-07-31 DOI: 10.1016/j.molcel.2024.07.003

引用次数: 0