MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3

National Science Review - Tập 7 Số 3 - Trang 671-685 - 2020
Chuanyin Li1,2,3, Wenli Lü1,2, Liguang Yang4,1,2,3, Zhengwei Li1,2,3, Xiaoyi Zhou5, Rong Guo1,2,3, Junqi Wang1,2, Zhe Wu6, Zhixia Dong1,2, Guang Ning7, Yujiang Geno Shi8,9, Yinmin Gu10, Peng Chen1,2,3, Zijian Hao1,2,3, Tianting Han1,2,3, Meiqiang Yang1,2,3, Wei Wang1,2, Xuehui Huang5, Yixue Li4,1,2,3, Shan Gao10, Ronggui Hu11,1,2,3
1Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
3University of Chinese Academy of Sciences, Beijing, 100049, China
4CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
5College of Life Sciences, Shanghai Normal University, Shanghai 200234, China
6Center for Pituitary Tumor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200025, China
7Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors and E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
8Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA
9Harvard Medical School Boston, MA 02115 USA
10CAS key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China
11Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China

Tóm tắt

AbstractCentral precocious puberty (CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone (GnRH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a ‘brake’ of mammalian puberty onset, but the underlying mechanisms remain as yet unknown. Here, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3–MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.

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Tài liệu tham khảo

Gajdos, 2009, What controls the timing of puberty? An update on progress from genetic investigation, Curr Opin Endocrinol Diabetes Obes, 16, 16, 10.1097/MED.0b013e328320253c

Abreu, 2016, Pubertal development and regulation, Lancet Diabetes Endocrinol, 4, 254, 10.1016/S2213-8587(15)00418-0

Day, 2016, Physical and neurobehavioral determinants of reproductive onset and success, Nat Genet, 48, 617, 10.1038/ng.3551

Golub, 2008, Public health implications of altered puberty timing, Pediatrics, 121, S218, 10.1542/peds.2007-1813G

Bessa, 2018, Methylome profiling of healthy and central precocious puberty girls, Clin Epigenet, 10, 146, 10.1186/s13148-018-0581-1

Toro, 2018, Hypothalamic epigenetics driving female puberty, J Neuroendocrinol, 30, e12589, 10.1111/jne.12589

Aylwin, 2019, Emerging genetic and epigenetic mechanisms underlying pubertal maturation in adolescence, J Res Adolesc, 29, 54, 10.1111/jora.12385

Abreu, 2013, Central precocious puberty caused by mutations in the imprinted gene MKRN3, N Engl J Med, 368, 2467, 10.1056/NEJMoa1302160

Yaqub, 2013, MKRN3 and central precocious puberty, Lancet Diabetes Endocrinol, 1, s15, 10.1016/S2213-8587(13)70041-X

Pastor, 2013, TETonic shift: biological roles of TET proteins in DNA demethylation and transcription, Nat Rev Mol Cell Biol, 14, 341, 10.1038/nrm3589

He, 2011, Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA, Science, 333, 1303, 10.1126/science.1210944

Zhang, 2013, Tet1 regulates adult hippocampal neurogenesis and cognition, Cell Stem Cell, 13, 237, 10.1016/j.stem.2013.05.006

Shen, 2013, 5-Hydroxymethylcytosine: generation, fate, and genomic distribution, Curr Opin Cell Biol, 25, 289, 10.1016/j.ceb.2013.02.017

Hendrich, 1999, Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes, Mamm Genome, 10, 906, 10.1007/s003359901112

Menafra, 2014, MBD2 and MBD3: elusive functions and mechanisms, Front Genet, 5, 428, 10.3389/fgene.2014.00428

Baubec, 2013, Methylation-dependent and -independent genomic targeting principles of the MBD protein family, Cell, 153, 480, 10.1016/j.cell.2013.03.011

Yildirim, 2011, Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells, Cell, 147, 1498, 10.1016/j.cell.2011.11.054

Brown, 2008, DNA demethylation induced by the methyl-CpG-binding domain protein MBD3, Gene, 420, 99, 10.1016/j.gene.2008.05.009

Peng, 2016, MBD3L2 promotes Tet2 enzymatic activity for mediating 5-methylcytosine oxidation, J Cell Sci, 129, 1059, 10.1242/jcs.179044

Cukier, 2010, Novel variants identified in methyl-CpG-binding domain genes in autistic individuals, Neurogenetics, 11, 291, 10.1007/s10048-009-0228-7

Sansom, 2007, Mechanisms of disease: methyl-binding domain proteins as potential therapeutic targets in cancer, Nat Rev Clin Oncol, 4, 305, 10.1038/ncponc0812

Hainer, 2016, DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells, Elife, 5, e21964, 10.7554/eLife.21964

Rais, 2013, Deterministic direct reprogramming of somatic cells to pluripotency, Nature, 502, 65, 10.1038/nature12587

dos Santos, 2014, MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner, Cell Stem Cell, 15, 102, 10.1016/j.stem.2014.04.019

Deshaies, 2009, RING domain E3 ubiquitin ligases, Annu Rev Biochem, 78, 399, 10.1146/annurev.biochem.78.101807.093809

Liu, 2014, Ubiquitylation of autophagy receptor Optineurin by HACE1 activates selective autophagy for tumor suppression, Cancer Cell, 26, 106, 10.1016/j.ccr.2014.05.015

Iwai, 2014, Ubiquitin chain elongation: an intriguing strategy, Mol Cell, 56, 189, 10.1016/j.molcel.2014.10.009

Hershko, 1998, The ubiquitin system, Annu Rev Biochem, 67, 425, 10.1146/annurev.biochem.67.1.425

Kerscher, 2006, Modification of proteins by ubiquitin and ubiquitin-like proteins, Annu Rev Cell Dev Biol, 22, 159, 10.1146/annurev.cellbio.22.010605.093503

Husnjak, 2012, Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions, Annu Rev Biochem, 81, 291, 10.1146/annurev-biochem-051810-094654

Cui, 2016, MBD3 mediates epigenetic regulation on EPAS1 promoter in cancer, Tumor Biol, 37, 13455, 10.1007/s13277-016-5237-1

Chen, 2014, Diversity of two forms of DNA methylation in the brain, Front Genet, 5, 46, 10.3389/fgene.2014.00046

Latronico, 2016, Causes, diagnosis, and treatment of central precocious puberty, Lancet Diabetes Endocrinol, 4, 265, 10.1016/S2213-8587(15)00380-0

Shin, 2016, An update on the genetic causes of central precocious puberty, Ann Pediatr Endocrinol Metab, 21, 66, 10.6065/apem.2016.21.2.66

Abreu, 2015, A new pathway in the control of the initiation of puberty: the MKRN3 gene, J Mol Endocrinol, 54, R131, 10.1530/JME-14-0315

Schreiner, 2014, MKRN3 Mutations in familial central precocious puberty, Horm Res Paediatr, 82, 122, 10.1159/000362815

Lu, 2018, A novel mutation in 5'-UTR of Makorin ring finger 3 gene associated with the familial precocious puberty, Acta Biochim Biophys Sin (Shanghai), 50, 1291, 10.1093/abbs/gmy124

Heras, 2019, Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3, PLoS Biol, 17, e3000532, 10.1371/journal.pbio.3000532

Bessa, 2017, High frequency of MKRN3 mutations in male central precocious puberty previously classified as idiopathic, Neuroendocrinology, 105, 17, 10.1159/000446963

Zhang, 2016, MiR-134-Mbd3 axis regulates the induction of pluripotency, J Cell Mol Med, 20, 1150, 10.1111/jcmm.12805

Roloff, 2003, Comparative study of methyl-CpG-binding domain proteins, BMC Genomics, 4, 1, 10.1186/1471-2164-4-1

Du, 2015, Methyl-CpG-binding domain proteins: readers of the epigenome, Epigenomics, 7, 1051, 10.2217/epi.15.39

Zhu, 2004, Genetic and epigenetic analyses of MBD3 in colon and lung cancer, Br J Cancer, 90, 1972, 10.1038/sj.bjc.6601776

Fraga, 2003, The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties, Nucleic Acids Res, 31, 1765, 10.1093/nar/gkg249

El-Osta, 2002, Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation, Mol Cell Biol, 22, 1844, 10.1128/MCB.22.6.1844-1857.2002

Lorincz, 2001, Methylation-mediated proviral silencing is associated with MeCP2 recruitment and localized histone H3 deacetylation, Mol Cell Biol, 21, 7913, 10.1128/MCB.21.23.7913-7922.2001

St Pourcain, 2013, Common variation contributes to the genetic architecture of social communication traits, Mol Autism, 4, 34, 10.1186/2040-2392-4-34

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National Science Review

Tập 7 Số 3

671-685

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