The stage-specific regulation of ameloblastin and enamelin by the distinct nuclear factors
不同核因子对成釉素和釉质的阶段特异性调节
基本信息
- 批准号:10804126
- 负责人:
- 金额:$ 48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-06 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AT Rich SequenceATAC-seqAblationAcetylationAddressAffectAmeloblastsAmelogenesisAmelogenesis ImperfectaArchitectureBindingBinding ProteinsBinding SitesBiological MarkersBiologyBiomedical EngineeringCRISPR/Cas technologyCalciumCell LineCellsCharacteristicsChromatinComplexDNA BindingDataDental EnamelDepositionDevelopmentDown-RegulationEnamel FormationEnamel OrganEndocytosisEnhancersEnvironmental Risk FactorEpigenetic ProcessEpithelial CellsFractureFundingGene ClusterGene ExpressionGene Expression ProfileGenesGenetic TranscriptionGenome engineeringGenomicsGlutamineGrantHIF1A geneHardnessHigh Pressure Liquid ChromatographyHistone AcetylationHydrolysisHypoxiaIn VitroIon TransportKnowledgeMediatingModelingMolecular ConformationMusNatural regenerationNuclearOrgan Culture TechniquesOxidative StressPeptide HydrolasesPeptidesProlineProtein BiochemistryRattusRegulationReporterRepressionResistanceResolutionRoleSiteSodiumTestingTissuesTooth eruptionTooth structureTranscriptional RegulationUp-RegulationVertebratesameloblastinamelogeninbasecalcificationcell regenerationenamel matrix proteinsenamelinextracellulargenetic signaturegenome-widegenomic locusin vivomineralizationnovelprotein degradationrepairedresilienceresponsescaffoldtranscription factortranscriptome sequencinguptake
项目摘要
Project Summary/Abstract
Cell identity is largely determined by specific epigenetic landscapes and transcriptional networks. Ameloblast is
the only epithelial cell that can generate calcified tissue during development, where preameloblasts (PABs) first
differentiate to the secretory ameloblasts (SABs) that synthesize and deposit enamel matrix proteins (EMPs) to
scaffold organic matrix, and then to the maturation ameloblasts (MABs) that hydrolyze, endocytose EMPs, and
transport ions to mineralize enamel. To bioengineer enamel, a nonregenerative tissue, we must understand the
transcriptional regulation of ameloblasts that has been limited due to a loss of ameloblasts after the tooth
eruption and a lack of cell line fully recapitulating the characteristics of ameloblasts. Previous fundings allow us
to establish a novel and comprehensive list of genes significant to each developmental stage of ameloblasts
across species and to explore the functions of chromatin organizer SATB1, and enamel matrix modeling
regulators -peptidase KLK4 and the major calcium transporter NCKX4- in the context of ameloblast
differentiation. These efforts resulted in a discovery that SATB1, KLK4, and NCKX4 all contribute to the
transcriptional regulation of ameloblastin (Ambn) and enamelin (Enam), encoding the major EMPs co-
upregulated in SABs and then co-downregulated in MABs. We found that ablation of SATB1, highly expressed
in PABs, repressed Ambn & Enam transcription and H3K27ac level. Our organ culture showed that elevated
histone acetylation upregulated Ambn & Enam. An enhancer and base unpairing region (BUR, selective
SATB1 DNA binding site) have been predicted in the vicinity of Ambn & Enam. These data suggest that
SATB1 organizes chromatin conformation and poises a transcriptional complex to upregulate Ambn & Enam to
advance PABs to SABs. In the case of mice lacking Klk4 and Nckx4—the causative genes for amelogenesis
imperfecta—we found a retention of proline/glutamine (P/G)-rich EMPs resulting from defective hydrolysis.
These Nckx4-/- and Klk4-/- MABs had upregulated Ambn & Enam and downregulated Hif1a. In vitro studies
showed that P/G-rich peptides downregulated Ambn & Enam and upregulated Hif1a. Our RNA-seq analyses
revealed that HIF1A, a transcription factor regulating cell responses to oxidative stress, had a 6-fold
upregulation in MABs vs SABs, reflecting MAB’s robust anti-oxidative capacity to continuously provide energy
for ion transport and protein degradation. These data suggest that retake of P/G-rich peptides upregulate
Hif1a, which in turn downregulate Ambn & Enam. Our in vivo and in vitro studies allow us to hypothesize that
the dynamic expression of Ambn & Enam in the two major functional stages of ameloblasts is coordinately
regulated by distinct factors chromatin organizer SATB1 and transcription factor HIF1A. This hypothesis will be
addressed by specific aim 1: To determine the roles of SATB1 as a pioneer factor in PABs to poise the
enhancer establishment for activating the transcription of Ambn & Enam gene in SABs; and specific aim 2: To
determine the regulatory roles of HIF1A on Ambn & Enam expression and enamel formation.
项目总结/文摘
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.
TRPM7介导的HAT-7成成木细胞中的钙转运。
- DOI:10.3390/ijms22083992
- 发表时间:2021-04-13
- 期刊:
- 影响因子:5.6
- 作者:Kádár K;Juhász V;Földes A;Rácz R;Zhang Y;Löchli H;Kató E;Köles L;Steward MC;DenBesten P;Varga G;Zsembery Á
- 通讯作者:Zsembery Á
Sodium/(calcium + potassium) exchanger NCKX4 optimizes KLK4 activity in the enamel matrix microenvironment to regulate ECM modeling.
- DOI:10.3389/fphys.2023.1116091
- 发表时间:2023
- 期刊:
- 影响因子:4
- 作者:
- 通讯作者:
WDR72 regulates vesicle trafficking in ameloblasts.
- DOI:10.1038/s41598-022-06751-1
- 发表时间:2022-02-18
- 期刊:
- 影响因子:4.6
- 作者:Katsura K;Nakano Y;Zhang Y;Shemirani R;Li W;Den Besten P
- 通讯作者:Den Besten P
A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix.
- DOI:10.1002/jbmr.4329
- 发表时间:2021-09
- 期刊:
- 影响因子:6.2
- 作者:Huang, Yulei;Bai, Yushi;Chang, Chih;Bacino, Margot;Cheng, Ieong Cheng;Li, Li;Habelitz, Stefan;Li, Wu;Zhang, Yan
- 通讯作者:Zhang, Yan
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Yan Zhang其他文献
Yan Zhang的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Yan Zhang', 18)}}的其他基金
High Urinary Phosphate Induces TLR4-mediated Inflammation and Cystogenesis in Polycystic Kidney Disease
高尿磷酸盐诱导多囊肾病中 TLR4 介导的炎症和囊肿发生
- 批准号:
10730615 - 财政年份:2023
- 资助金额:
$ 48万 - 项目类别:
The stage-specific regulation of ameloblastin and enamelin by the distinct nuclear factors
不同核因子对成釉素和釉质的阶段特异性调节
- 批准号:
10645781 - 财政年份:2022
- 资助金额:
$ 48万 - 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
- 批准号:
10454868 - 财政年份:2020
- 资助金额:
$ 48万 - 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
- 批准号:
10664972 - 财政年份:2020
- 资助金额:
$ 48万 - 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
- 批准号:
10026656 - 财政年份:2020
- 资助金额:
$ 48万 - 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
- 批准号:
10792662 - 财政年份:2020
- 资助金额:
$ 48万 - 项目类别:
Generation of DNA memory by bacterial CRISPR-Cas9 systems
通过细菌 CRISPR-Cas9 系统生成 DNA 记忆
- 批准号:
10227166 - 财政年份:2020
- 资助金额:
$ 48万 - 项目类别:
Investigating the Role of BACE2 in Melanocyte Development and Melanoma Progression
研究 BACE2 在黑色素细胞发育和黑色素瘤进展中的作用
- 批准号:
9814738 - 财政年份:2019
- 资助金额:
$ 48万 - 项目类别:
Regulation of enamel matrix protein secretion in ameloblasts
成釉细胞釉质基质蛋白分泌的调节
- 批准号:
10192703 - 财政年份:2017
- 资助金额:
$ 48万 - 项目类别:
Investigating the Role of BACE2 in Melanocyte Development and Melanoma Progression
研究 BACE2 在黑色素细胞发育和黑色素瘤进展中的作用
- 批准号:
9229644 - 财政年份:2016
- 资助金额:
$ 48万 - 项目类别:
相似国自然基金
基于ATAC-seq与DNA甲基化测序探究染色质可及性对莲两生态型地下茎适应性分化的作用机制
- 批准号:
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
利用ATAC-seq联合RNA-seq分析TOP2A介导的HCC肿瘤细胞迁移侵
袭的机制研究
- 批准号:
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
面向图神经网络ATAC-seq模体识别的最小间隔单细胞聚类研究
- 批准号:62302218
- 批准年份:2023
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
基于ATAC-seq策略挖掘穿心莲基因组中调控穿心莲内酯合成的增强子
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
基于单细胞ATAC-seq技术的C4光合调控分子机制研究
- 批准号:
- 批准年份:2021
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于ATAC-seq技术研究交叉反应物质197调控TFEB介导的自噬抑制子宫内膜异位症侵袭的分子机制
- 批准号:82001520
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
靶向治疗动态调控肺癌细胞DNA可接近性的ATAC-seq分析
- 批准号:81802809
- 批准年份:2018
- 资助金额:21.0 万元
- 项目类别:青年科学基金项目
运用ATAC-seq技术分析染色质可接近性对犏牛初级精母细胞基因表达的调控作用
- 批准号:31802046
- 批准年份:2018
- 资助金额:27.0 万元
- 项目类别:青年科学基金项目
基于ATAC-seq和RNA-seq研究CWIN调控采后番茄果实耐冷性作用机制
- 批准号:31801915
- 批准年份:2018
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
基于ATAC-seq高精度预测染色质相互作用的新方法和基于增强现实的3D基因组数据可视化
- 批准号:31871331
- 批准年份:2018
- 资助金额:59.0 万元
- 项目类别:面上项目
相似海外基金
Project #2 Integrated single-nucleus multi-omics (ATAC-seq+RNA-seq or chromatin accessibility + RNA-seq) of human TGs
项目
- 批准号:
10806548 - 财政年份:2023
- 资助金额:
$ 48万 - 项目类别:
A transposase system for integrative ChIP-exo and ATAC-seq analysis at single-cell resolution
用于单细胞分辨率综合 ChIP-exo 和 ATAC-seq 分析的转座酶系统
- 批准号:
10210424 - 财政年份:2018
- 资助金额:
$ 48万 - 项目类别:
EAPSI: Developing Single Nucleus ATAC-seq to Map the Ageing Epigenome
EAPSI:开发单核 ATAC-seq 来绘制衰老表观基因组图谱
- 批准号:
1714070 - 财政年份:2017
- 资助金额:
$ 48万 - 项目类别:
Fellowship Award
A cloud-based learning module to analyze ATAC-seq and single cell ATAC-seq data
基于云的学习模块,用于分析 ATAC-seq 和单细胞 ATAC-seq 数据
- 批准号:
10558379 - 财政年份:2001
- 资助金额:
$ 48万 - 项目类别:














{{item.name}}会员




