title: Notch signaling genes: myogenic DNA hypomethylation and 5-hydroxymethylcytosine.
abstract: Notch intercellular signaling is critical for diverse developmental pathways and for homeostasis in various types of stem cells and progenitor cells. Because Notch gene products need to be precisely regulated spatially and temporally, epigenetics is likely to help control expression of Notch signaling genes. Reduced representation bisulfite sequencing (RRBS) indicated significant hypomethylation in myoblasts, myotubes, and skeletal muscle vs. many nonmuscle samples at intragenic or intergenic regions of the following Notch receptor or ligand genes: NOTCH1, NOTCH2, JAG2, and DLL1. An enzymatic assay of sites in or near these genes revealed unusually high enrichment of 5-hydroxymethylcytosine (up to 81%) in skeletal muscle, heart, and cerebellum. Epigenetics studies and gene expression profiles suggest that hypomethylation and/or hydroxymethylation help control expression of these genes in heart, brain, myoblasts, myotubes, and within skeletal muscle myofibers. Such regulation could promote cell renewal, cell maintenance, homeostasis, and a poised state for repair of tissue damage.
authors.affiliation: New England Biolabs; Ipswich, MA USA.
authors.forename: Jolyon
authors.initials: J
authors.lastname: Terragni
authors.affiliation: New England Biolabs; Ipswich, MA USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: New England Biolabs; Ipswich, MA USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: New England Biolabs; Ipswich, MA USA.
authors.forename: Sriharsa
authors.initials: S
authors.lastname: Pradhan
authors.affiliation: Institute for Genome Sciences & Policy; Duke University; Durham, NC USA.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute for Genome Sciences & Policy; Duke University; Durham, NC USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.affiliation: Tulane Cancer Center and Department of Mathematics; Tulane Health Sciences Center and Tulane University; New Orleans, LA USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lacey
authors.affiliation: Program in Human Genetics; Tulane Cancer Center; Center for Bioinformatics and Genomics; Tulane Health Sciences Center; New Orleans, LA USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ehrlich
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000368:Aged; D000369:Aged, 80 and over; D002531:Cerebellum / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D049308:Dioxygenases; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: 5-hydroxymethylcytosine; DNA methylation; DNaseI hypersensitivity; brain; enhancers; heart; histone H3 methylation; muscle; myoblasts; notch signaling