DMRT1: An Ancient Sexual Regulator Required for Human Gonadogenesis.
DMRT1: An Ancient Sexual Regulator Required for Human Gonadogenesis.
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DOI：
10.1159/000518272
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Murphy MW
中科院分区：
文献类型：
--
作者：
Zarkower D;Murphy MW
与无脊椎动物的性调节因子doublex和mab-3相关的转录调节因子在后生动物中普遍存在，并在大多数动物群体中控制性别。这些DMRT基因中有七个在哺乳动物中发现，小鼠遗传学表明，其中一个Dmrt 1在生殖细胞和体细胞的睾丸分化中起着至关重要的作用。缺失，最近，点突变影响人类DMRT 1已证明，其杂合性与46，XY完全性腺发育不全。我们对DMRT 1在睾丸中的功能的详细了解，本次审查的重点，来自小鼠的研究，这表明DMRT 1是必不可少的男性体细胞和生殖细胞分化和维持分化后的男性体细胞的命运。此外，异位DMRT 1可以将分化的雌性颗粒细胞重编程为雄性支持样细胞。DMRT 1控制性细胞命运的能力可能来自至少三种特性。首先，DMRT 1在功能上与另一个关键的男性性别调节因子SOX 9以及可能的其他蛋白质合作，以维持和重新编程性细胞的命运。第二，相关的，DMRT 1似乎作为一个先驱转录因子，结合“封闭的”不可接近的染色质，并促进其开放，允许其他监管机构，包括SOX 9的结合。第三，DMRT 1通过一种非常不寻常的相互作用形式与DNA结合，并且可以以不同的化学计量结合。
Transcriptional regulators related to the invertebrate sexual regulators doublesex and mab-3 occur throughout metazoans and control sex in most animal groups. Seven of these DMRT genes are found in mammals, and mouse genetics has shown that one, Dmrt1, plays a crucial role in testis differentiation, both in germ cells and somatic cells. Deletions and, more recently, point mutations affecting human DMRT1 have demonstrated that its heterozygosity is associated with 46,XY complete gonadal dysgenesis. Most of our detailed knowledge of DMRT1 function in the testis, the focus of this review, derives from mouse studies, which have revealed that DMRT1 is essential for male somatic and germ cell differentiation and maintenance of male somatic cell fate after differentiation. Moreover, ectopic DMRT1 can reprogram differentiated female granulosa cells into male Sertoli-like cells. The ability of DMRT1 to control sexual cell fate likely derives from at least three properties. First, DMRT1 functionally collaborates with another key male sex regulator, SOX9, and possibly other proteins to maintain and reprogram sexual cell fate. Second, and related, DMRT1 appears to function as a pioneer transcription factor, binding “closed” inaccessible chromatin and promoting its opening to allow binding by other regulators including SOX9. Third, DMRT1 binds DNA by a highly unusual form of interaction and can bind with different stoichiometries.
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影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
4.1
作者：
Buonocore, Federica;Clifford-Mobley, Oliver;Achermann, John C.
通讯作者：
Achermann, John C.
影响因子：
64.8
作者：
Andersson, Lisa S.;Larhammar, Martin;Memic, Fatima;Wootz, Hanna;Schwochow, Doreen;Rubin, Carl-Johan;Patra, Kalicharan;Arnason, Thorvaldur;Wellbring, Lisbeth;Hjalm, Goran;Imsland, Freyja;Petersen, Jessica L.;McCue, Molly E.;Mickelson, James R.;Cothran, Gus;Ahituv, Nadav;Roepstorff, Lars;Mikko, Sofia;Vallstedt, Anna;Lindgren, Gabriella;Andersson, Leif;Kullander, Klas
通讯作者：
Kullander, Klas
影响因子：
5.3
作者：
Balciuniene, Jorune;Bardwell, Vivian J.;Zarkower, David
通讯作者：
Zarkower, David
影响因子：
9.8
作者：
Flejter, WL;Fergestad, J;Chandrasekharappa, S
通讯作者：
Chandrasekharappa, S