The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.
The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.
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DOI：
10.1038/s41467-020-20511-7
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发表时间：
2021-01-11
影响因子：
16.6
通讯作者：
Lee JW
中科院分区：
文献类型：
--
作者：
Huisman C;Kim YA;Jeon S;Shin B;Choi J;Lim SJ;Youn SM;Park Y;K C M;Kim S;Lee SK;Lee S;Lee JW
In humans, inactivating mutations in MLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our two Mll4 mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency of Mll4 results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production in Mll4 mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice. Mutations in the MLL4 gene can cause Kabuki syndrome, whose underlying molecular mechanisms are unclear. Here, the authors show that Mll4 epigenetically regulates the transcriptional program leading to the formation of GHRH-neurons in the developing mouse hypothalamus.
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影响因子：
64.8
作者：
Lasko LM;Jakob CG;Edalji RP;Qiu W;Montgomery D;Digiammarino EL;Hansen TM;Risi RM;Frey R;Manaves V;Shaw B;Algire M;Hessler P;Lam LT;Uziel T;Faivre E;Ferguson D;Buchanan FG;Martin RL;Torrent M;Chiang GG;Karukurichi K;Langston JW;Weinert BT;Choudhary C;de Vries P;Van Drie JH;McElligott D;Kesicki E;Marmorstein R;Sun C;Cole PA;Rosenberg SH;Michaelides MR;Lai A;Bromberg KD
通讯作者：
Bromberg KD
影响因子：
--
作者：
Biebermann, Heike;Kuhnen, Peter;Krude, Heiko
通讯作者：
Krude, Heiko
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.5
作者：
Kim, Dae-Hwan;Rhee, Jennifer Chiyeon;Yeo, Sujeong;Shen, Rongkun;Lee, Soo-Kyung;Lee, Jae W.;Lee, Seunghee
通讯作者：
Lee, Seunghee