TY - JOUR AU - Belan, Ekaterina PY - 2013 DA - 2013/09/13 TI - LINEs of evidence: noncanonical DNA replication as an epigenetic determinant JO - Biology Direct SP - 22 VL - 8 IS - 1 AB - LINE-1 (L1) retrotransposons are repetitive elements in mammalian genomes. They arecapable of synthesizing DNA on their own RNA templates by harnessing reversetranscriptase (RT) that they encode. Abundantly expressed full-length L1s and theirRT are found to globally influence gene expression profiles, differentiation state,and proliferation capacity of early embryos and many types of cancer, albeit by yetunknown mechanisms. They are essential for the progression of early development andthe establishment of a cancer-related undifferentiated state. This raises importantquestions regarding the functional significance of L1 RT in these cell systems.Massive nuclear L1-linked reverse transcription has been shown to occur in mousezygotes and two-cell embryos, and this phenomenon is purported to be DNA replicationindependent. This review argues against this claim with the goal of understanding thenature of this phenomenon and the role of L1 RT in early embryos and cancers.Available L1 data are revisited and integrated with relevant findings accumulated inthe fields of replication timing, chromatin organization, and epigenetics, bringingtogether evidence that strongly supports two new concepts. First, noncanonicalreplication of a portion of genomic full-length L1s by means of L1 RNP-driven reversetranscription is proposed to co-exist with DNA polymerase-dependent replication ofthe rest of the genome during the same round of DNA replication in embryonic andcancer cell systems. Second, the role of this mechanism is thought to be epigenetic;it might promote transcriptional competence of neighboring genes linked toundifferentiated states through the prevention of tethering of involved L1s to thenuclear periphery. From the standpoint of these concepts, several hithertoinexplicable phenomena can be explained. Testing methods for the model areproposed. SN - 1745-6150 UR - https://doi.org/10.1186/1745-6150-8-22 DO - 10.1186/1745-6150-8-22 ID - Belan2013 ER -