期刊
GENOMICS
卷 109, 期 3-4, 页码 265-273出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2017.04.008
关键词
CpG-rich motifs; Gene regulation; Imprinting mechanisms; KMT2A; Protein networks; TRIM28/KAP1
Mammalian genomes include DNA segments that are imprinted (CpG-methylated) only on one of the two parental chromosomes, leading to parent-of-origin-specific gene expression. The process is regulated by Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). Previously, ZFP57 was shown to recognize a methylated hexanucleotide in ICRs to maintain allele-specific gene repression. In Bioinformatics analyses, I found that the hexamer occurred frequently in mouse chromosomal DNA, suggesting that beside the ZFP57 binding site (ZFBS), ICRs contained sequence features with unknown characteristics. To identify such features, I examined chromosomal abundance of motifs in which the length of the hexamer was extended by one or several nucleotides. Results led to the discovery of a group of functionally significant composite DNA elements (ZFBS-Morph overlaps) thatmay play dual roles in the regulation of allele-specific gene expression. Importantly, results of genome-wide evaluations revealed that nearly 90% of the gDMRs included closely-spaced ZFBS-Morph overlaps. (C) 2017 Published by Elsevier Inc.
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