@article{0f0e86b305214d1eb2693a96f677a2f2,
title = "HP1 Is Involved in Regulating the Global Impact of DNA Methylation on Alternative Splicing",
abstract = "The global impact of DNA methylation on alternative splicing is largely unknown. Using a genome-wide approach in wild-type and methylation-deficient embryonic stem cells, we found that DNA methylation can either enhance or silence exon recognition and affects the splicing of more than 20% of alternative exons. These exons are characterized by distinct genetic and epigenetic signatures. Alternative splicing regulation of a subset of these exons can be explained by heterochromatin protein 1 (HP1), which silences or enhances exon recognition in a position-dependent manner. We constructed an experimental system using site-specific targeting of a methylated/unmethylated gene and demonstrate a direct causal relationship between DNA methylation and alternative splicing. HP1 regulates this gene's alternative splicing in a methylation-dependent manner by recruiting splicing factors to its methylated form. Our results demonstrate DNA methylation's significant global influence on mRNA splicing and identify a specific mechanism of splicing regulation mediated by HP1.",
author = "Ahuvi Yearim and Sahar Gelfman and Ronna Shayevitch and Shai Melcer and Ohad Glaich and Mallm, {Jan Philipp} and Malka Nissim-Rafinia and Cohen, {Ayelet Hashahar S.} and Karsten Rippe and Eran Meshorer and Gil Ast",
note = "Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = feb,
day = "24",
doi = "10.1016/j.celrep.2015.01.038",
language = "אנגלית",
volume = "10",
pages = "1122--1134",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}
