Wolf-Hirschhorn syndrome candidate 1 (Whsc1) methyltransferase signals via a Pitx2-miR-23/24 axis to effect tooth development.
Wolf-Hirschhorn syndrome candidate 1 (Whsc1) methyltransferase signals via a Pitx2-miR-23/24 axis to effect tooth development.
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DOI：
10.1016/j.jbc.2023.105324
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发表时间：
2023-11
影响因子：
4.8
通讯作者：
Amendt, Brad A.
中科院分区：
文献类型：
--
作者：
Su, Dan;Eliason, Steve;Sun, Zhao;Shao, Fan;Amendt, Brad A.
Wolf-Hirschhorn综合征（WHS）是一种由于4号染色体短臂部分缺失引起的发育障碍。WHS患者遭受口腔表现，包括唇腭裂，缺牙，和牛牙病。WHS候选1（WHSC 1）基因是一种H3 K36特异性甲基转移酶，在所有报道的WHS病例中均缺失。这种基因的突变也会导致患者的牙齿异常。然而，遗传异常和牙齿异常之间的相关性仍然存在争议。在我们的研究中，我们的目的是阐明WHSC 1在牙齿发育中的作用。我们通过免疫荧光染色分析了小鼠切牙和磨牙发育过程中Whsc 1的表达模式，发现Whsc 1的表达随着牙齿发育的进行而减少。利用实时定量逆转录PCR、蛋白质印迹、染色质免疫沉淀和荧光素酶测定，我们确定了参与牙齿发育的初始转录因子Whsc 1和Pitx 2通过其基因启动子相互正向调节。已知miRNA在发育过程中转录后调节基因表达。我们以前报道过miR-23 a/B和miR-24-1/2在成熟牙胚中高表达。有趣的是，我们在这里证明了这两个miR直接靶向Whsc 1并抑制其表达。此外，该miR簇也受到Pitx 2的负调控。我们发现这两个miR和Whsc 1的表达在小鼠下颌骨发育过程中呈负相关。总之，我们的研究结果提供了新的见解Whsc 1在调节牙齿发育的潜在作用和WHS牙齿缺陷的潜在分子机制。
Wolf-Hirschhorn syndrome (WHS) is a developmental disorder attributed to a partial deletion on the short arm of chromosome 4. WHS patients suffer from oral manifestations including cleft lip and palate, hypodontia, and taurodontism. WHS candidate 1 (WHSC1) gene is a H3K36-specific methyltransferase that is deleted in every reported case of WHS. Mutation in this gene also results in tooth anomalies in patients. However, the correlation between genetic abnormalities and the tooth anomalies has remained controversial. In our study, we aimed to clarify the role of WHSC1 in tooth development. We profiled the Whsc1 expression pattern during mouse incisor and molar development by immunofluorescence staining and found Whsc1 expression is reduced as tooth development proceeds. Using real-time quantitative reverse transcription PCR, Western blot, chromatin immunoprecipitation, and luciferase assays, we determined that Whsc1 and Pitx2, the initial transcription factor involved in tooth development, positively and reciprocally regulate each other through their gene promoters. miRNAs are known to regulate gene expression posttranscriptionally during development. We previously reported miR-23a/b and miR-24-1/2 were highly expressed in the mature tooth germ. Interestingly, we demonstrate here that these two miRs directly target Whsc1 and repress its expression. Additionally, this miR cluster is also negatively regulated by Pitx2. We show the expression of these two miRs and Whsc1 are inversely correlated during mouse mandibular development. Taken together, our results provide new insights into the potential role of Whsc1 in regulating tooth development and a possible molecular mechanism underlying the dental defects in WHS.
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影响因子：
3.9
作者：
Limeres J;Serrano C;De Nova JM;Silvestre-Rangil J;Machuca G;Maura I;Cruz Ruiz-Villandiego J;Diz P;Blanco-Lago R;Nevado J;Diniz-Freitas M
通讯作者：
Diniz-Freitas M
影响因子：
3
作者：
CHEN, LS;COUWENHOVEN, RI;SNEAD, ML
通讯作者：
SNEAD, ML
影响因子：
7.6
作者：
Cao H;Wang J;Li X;Florez S;Huang Z;Venugopalan SR;Elangovan S;Skobe Z;Margolis HC;Martin JF;Amendt BA
通讯作者：
Amendt BA
DOI：
10.3390/children8090751
发表时间：
2021-08-30
期刊：
Children (Basel, Switzerland)
影响因子：
--
作者：
Gavril EC;Luca AC;Curpan AS;Popescu R;Resmerita I;Panzaru MC;Butnariu LI;Gorduza EV;Gramescu M;Rusu C
通讯作者：
Rusu C
影响因子：
2.5
作者：
Gage, PJ;Suh, H;Camper, SA
通讯作者：
Camper, SA