Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood

被引：20

作者：

Buckley, Lauren ^{[1
]}

Lacey, Michelle ^{[2
,3
]}

Ehrlich, Melanie ^{[4
]}

机构：

[1] Tulane Univ, Hlth Sci Ctr, Human Genet Program, New Orleans, LA 70112 USA

[2] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70112 USA

[3] Tulane Univ, Dept Math, New Orleans, LA 70112 USA

[4] Tulane Univ, Hlth Sci Ctr, Tulane Canc Ctr, Human Genet Program,Ctr Bioinformat & Genom, New Orleans, LA 70112 USA

来源：

EPIGENOMICS | 2016年 / 8卷 / 01期

关键词：

alternative promoters; CTCF; DNA methylation; enhancers; G-quadruplex; histone modification; muscle; myotonic dystrophy; sperm DNA; testis; PROTEIN-KINASE DMPK; CTCF-BINDING SITES; DNA METHYLATION; G-QUADRUPLEXES; MICE LACKING; MUSCLE; TRANSCRIPTION; EXPRESSION; MOUSE; RNA;

D O I：

10.2217/epi.15.104

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aim: Identify epigenetic marks in the vicinity of DMPK (linked to myotonic dystrophy, DM1) that help explain tissue-specific differences in its expression. Materials & methods: At DMPK and its flanking genes (DMWD, SIX5, BHMG1 and RSPH6A), we analyzed many epigenetic and transcription profiles from myoblasts, myotubes, skeletal muscle, heart and 30 nonmuscle samples. Results: In the DMPK gene neighborhood, muscle-associated DNA hypermethylation and hypomethylation, enhancer chromatin, and CTCF binding were seen. Myogenic DMPK hypermethylation correlated with high expression and decreased alternative promoter usage. Testis/sperm hypomethylation of BHMG1 and RSPH6A was associated with testis-specific expression. G-quadruplex (G4) motifs and sperm-specific hypomethylation were found near the DM1-linked CTG repeats within DMPK. Conclusion: Tissue-specific epigenetic features in DMPK and neighboring genes help regulate its expression. G4 motifs in DMPK DNA and RNA might contribute to DM1 pathology.

引用

页码：13 / 31

页数：19

共 76 条

[1] ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters [J].

Bailey, Swneke D. ;

Zhang, Xiaoyang ;

Desai, Kinjal ;

Aid, Malika ;

Corradin, Olivia ;

Iari, Richard Cowper-Sal ;

Akhtar-Zaidi, Batool ;

Scacheri, Peter C. ;

Haibe-Kains, Benjamin ;

Lupien, Mathieu .

NATURE COMMUNICATIONS, 2015, 6

[2] Myotonic dystrophy protein kinase is involved in the modulation of the Ca2+ homeostasis in skeletal muscle cells [J].

Benders, AAGM ;

Groenen, PJTA ;

Oerlemans, FTJJ ;

Veerkamp, JH ;

Wieringa, B .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (06) :1440-1447

[3] DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model [J].

Berul, CI ;

Maguire, CT ;

Aronovitz, MJ ;

Greenwood, J ;

Miller, C ;

Gehrmann, J ;

Housman, D ;

Mendelsohn, ME ;

Reddy, S .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (04) :R1-R7

[4] Cis-acting modifiers of expanded CAG CTG triplet repeat expandability:: associations with flanking GC content and proximity to CpG islands [J].

Brock, GJR ;

Anderson, NH ;

Monckton, DG .

HUMAN MOLECULAR GENETICS, 1999, 8 (06) :1061-1067

[5] Transcriptionally Repressive Chromatin Remodelling and CpG Methylation in the Presence of Expanded CTG-Repeats at the DM1 Locus [J].

Brouwer, Judith Rixt ;

Huguet, Aline ;

Nicole, Annie ;

Munnich, Arnold ;

Gourdon, Genevieve .

JOURNAL OF NUCLEIC ACIDS, 2013, 2013

[6] Overexpression of myotonic dystrophy kinase in BC(3)H1 cells induces the skeletal muscle phenotype [J].

Bush, EW ;

Taft, CS ;

Meixell, GE ;

Perryman, MB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (01) :548-552

[7] Skin features in myotonic dystrophy type 1: An observational study [J].

Campanati, A. ;

Giannoni, M. ;

Buratti, L. ;

Cagnetti, C. ;

Giuliodori, K. ;

Ganzetti, G. ;

Silvestrini, M. ;

Provinciali, L. ;

Offidani, A. .

NEUROMUSCULAR DISORDERS, 2015, 25 (05) :409-413

[8] Genome-wide MyoD Binding in Skeletal Muscle Cells: A Potential for Broad Cellular Reprogramming [J].

Cao, Yi ;

Yao, Zizhen ;

Sarkar, Deepayan ;

Lawrence, Michael ;

Sanchez, Gilson J. ;

Parker, Maura H. ;

MacQuarrie, Kyle L. ;

Davison, Jerry ;

Morgan, Martin T. ;

Ruzzo, Walter L. ;

Gentleman, Robert C. ;

Tapscott, Stephen J. .

DEVELOPMENTAL CELL, 2010, 18 (04) :662-674

[9] Regulation of gene expression in vertebrate skeletal muscle [J].

Carvajal, Jaime J. ;

Rigby, Peter W. J. .

EXPERIMENTAL CELL RESEARCH, 2010, 316 (18) :3014-3018

[10] Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues [J].

Castel, Arturo Lopez ;

Nakamori, Masayuki ;

Tome, Stephanie ;

Chitayat, David ;

Gourdon, Genevieve ;

Thornton, Charles A. ;

Pearson, Christopher E. .

HUMAN MOLECULAR GENETICS, 2011, 20 (01) :1-15

← 1 2 3 4 5 6 7 8 →