文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

溴结构域因子 5 是利什曼原虫转录的必需调节因子。

Bromodomain factor 5 is an essential regulator of transcription in Leishmania.

机构信息

York Biomedical Research Institute, Department of Biology, University of York, York, UK.

GSK Global Health, Tres Cantos, 28760, Madrid, Spain.

出版信息

Nat Commun. 2022 Jul 13;13(1):4071. doi: 10.1038/s41467-022-31742-1.

DOI:10.1038/s41467-022-31742-1
PMID:35831302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9279504/
Abstract

Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1-5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.

摘要

利什曼原虫是一种单细胞寄生虫，可引起人类和动物疾病。与其他动基体目生物一样，它们具有由组蛋白变体和组蛋白赖氨酸乙酰化定义的大型转录起始区（TSR）。这些染色质标记的细胞解释尚不清楚。在利什曼原虫基因组中发现了八个溴结构域因子，即乙酰化赖氨酸的读取模块。使用 L. mexicana，Cas9 驱动的基因缺失表明 BDF1-5 对前鞭毛体是必需的。可二聚化、分裂 Cre 重组酶（DiCre）诱导的 BDF5 基因缺失表明它对前鞭毛体和小鼠感染都是必需的。ChIP-seq 鉴定出 BDF5 在 TSR 处富集。XL-BioID 邻近蛋白质组学显示 BDF5 景观富含 BDFs、HAT2、参与转录活性和 RNA 处理的蛋白质；揭示了一个保守的动基体转录调控因子（CRKT）复合物。BDF5 的诱导缺失导致 RNA 聚合酶 II 转录的全局减少。我们的结果表明，利什曼原虫需要通过富含溴结构域的 CRKT 复合物来解释组蛋白乙酰化标记，以维持正常的基因表达和细胞活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/6646d8edede2/41467_2022_31742_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/654d64db5414/41467_2022_31742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/ba5c6d2e83d9/41467_2022_31742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/dbf010612cb0/41467_2022_31742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/b57c66c54a55/41467_2022_31742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/bbef8548c2bf/41467_2022_31742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/22b4b883d3b1/41467_2022_31742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/6646d8edede2/41467_2022_31742_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/654d64db5414/41467_2022_31742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/ba5c6d2e83d9/41467_2022_31742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/dbf010612cb0/41467_2022_31742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/b57c66c54a55/41467_2022_31742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/bbef8548c2bf/41467_2022_31742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/22b4b883d3b1/41467_2022_31742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1e/9279504/6646d8edede2/41467_2022_31742_Fig7_HTML.jpg

相似文献

[1]
Bromodomain factor 5 is an essential regulator of transcription in Leishmania.

Nat Commun. 2022-7-13

[2]
Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery.

ACS Infect Dis. 2023-11-10

[3]
HAT2 mediates histone H4K4 acetylation and affects micrococcal nuclease sensitivity of chromatin in Leishmania donovani.

PLoS One. 2017-5-9

[4]
Cooperative binding of two acetylation marks on a histone tail by a single bromodomain.

Nature. 2009-10-1

[5]
Bromodomain Histone Readers and Cancer.

J Mol Biol. 2016-11-24

[6]
Histone H4 lysine 14 acetylation in Leishmania donovani is mediated by the MYST-family protein HAT4.

Microbiology (Reading). 2011-10-20

[7]
The bromodomain: from epigenome reader to druggable target.

Biochim Biophys Acta. 2014-8

[8]
Metabolically controlled histone H4K5 acylation/acetylation ratio drives BRD4 genomic distribution.

Cell Rep. 2021-7-27

[9]
Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation.

J Biol Chem. 2017-9-1

[10]
Interplay of bromodomain and histone acetylation in the regulation of p300-dependent genes.

Epigenetics. 2010-8-16

引用本文的文献

[1]
1,3,4-oxadiazoles as inhibitors of the atypical member of the BET family bromodomain factor 3 from (BDF3).

Front Microbiol. 2024-10-1

[2]
Identification of novel bromodomain inhibitors of bromodomain factor 2 (BDF2) using a fluorescence polarization-based high-throughput assay.

Antimicrob Agents Chemother. 2024-8-7

[3]
Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.

PLoS Pathog. 2024-7

[4]
Bromodomain Factor 5 as a Target for Antileishmanial Drug Discovery.

ACS Infect Dis. 2023-11-10

[5]
Chemical Inhibition of Bromodomain Proteins in Insect-Stage African Trypanosomes Perturbs Silencing of the Variant Surface Glycoprotein Repertoire and Results in Widespread Changes in the Transcriptome.

Microbiol Spectr. 2023-6-15

[6]
The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.

Front Cell Infect Microbiol. 2023

[7]
CLK1/CLK2-driven signalling at the Leishmania kinetochore is captured by spatially referenced proximity phosphoproteomics.

Commun Biol. 2022-11-28

[8]
Genomic Occupancy of the Bromodomain Protein Bdf3 Is Dynamic during Differentiation of African Trypanosomes from Bloodstream to Procyclic Forms.

mSphere. 2022-6-29

本文引用的文献

[1]
Phosphorylation-dependent BRD4 dimerization and implications for therapeutic inhibition of BET family proteins.

Commun Biol. 2021-11-9

[2]
Expanding Bromodomain Targeting into Neglected Parasitic Diseases.

ACS Infect Dis. 2021-11-12

[3]
A systematic analysis of chromatin factors identifies novel protein interaction networks associated with sites of transcription initiation and termination.

Genome Res. 2021-11

[4]
Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.

Nat Commun. 2021-2-23

[5]
Essential roles for deubiquitination in Leishmania life cycle progression.

PLoS Pathog. 2020-6-16

[6]
Distinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes.

Nat Commun. 2020-3-20

[7]
Rapid block of pre-mRNA splicing by chemical inhibition of analog-sensitive CRK9 in Trypanosoma brucei.

Mol Microbiol. 2020-6

[8]
Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone.

Nat Commun. 2019-12-17

[9]
Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity.

Genes Dev. 2019-11-21

[10]
Bromodomain biology and drug discovery.

Nat Struct Mol Biol. 2019-10-3

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索