[Frontiers in Bioscience E4, 2203-2225, January 1, 2012]

L1 expression and regulation in humans and rodents

James M. Rosser1, Wenfeng An1

1School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Endogenous L1 expression
3.1. Endogenous human L1 expression
3.1.1. Human cell lines
3.1.2. Human germ cell tumors
3.1.3. Human breast cancers
3.1.4. Human somatic and germline tissues
3.2. Endogenous rat L1 expression
3.3. Endogenous mouse L1 expression
3.3.1. Mouse cell lines
3.3.2. Mouse germ cells
3.3.3. Mouse somatic cells
4. Regulation of L1 expression
4.1. Transcription factors
4.2. DNA Methylation and PIWI/piRNA pathway
4.2.1. L1 methylation in cell lines and its correlation with L1 expression
4.2.2. L1 methylation in mouse tissues during development
4.2.3. Correlation of L1 methylation and expression during development
4.2.4. L1 expression in mice deficient in piRNA/DNA methylation pathways
4.3. Posttranscriptional regulation of L1 expression
4.3.1. Host factors for posttranscriptional regulation
4.3.2. RNA interference (RNAi)
4.3.3. piRNA-mediated posttranscriptional silencing in germ cells
4.3.4. Cytoplasmic sequestration of L1 ribonucleoprotein (RNP) complexes
5. L1 transgenic mouse models
5.1. L1 expression from transgenes
5.1.1. Expression in germ cells
5.1.2. Expression in preimplantation embryos
5.1.3. Expression in somatic tissues
5.2. L1 retrotransposition in transgenic models
5.2.1. Retrotransposition in germ cells
5.2.2. Retrotransposition in preimplantation embryos
5.2.3. Retrotransposition during postimplantation and postnatal development
5.2.4. Retrotransposition in the brain
5.3. Challenges and opportunities for L1 transgenic models
5.3.1. Are human and mouse L1 families similarly regulated in vivo?
5.3.2. Do L1 copy number and genomic location matter?
6. Perspective
7. Acknowledgments
8. References

1. ABSTRACT

Long interspersed elements type 1 (LINE-1s, or L1s) have impacted mammalian genomes at multiple levels. L1 transcription is mainly controlled by its 5' untranslated region (5'UTR), which differs significantly among active human and rodent L1 families. In this review, L1 expression and its regulation are examined in the context of human and rodent development. First, endogenous L1 expression patterns in three different species-human, rat, and mouse-are compared and contrasted. A detailed account of relevant experimental evidence is presented according to the source material, such as cell lines, tumors, and normal somatic and germline tissues from different developmental stages. Second, factors involved in the regulation of L1 expression at both transcriptional and posttranscriptional levels are discussed. These include transcription factors, DNA methylation, PIWI-interacting RNAs (piRNAs), RNA interference (RNAi), and posttranscriptional host factors. Similarities and differences between human and rodent L1s are highlighted. Third, recent findings from transgenic mouse models of L1 are summarized and contrasted with those from endogenous L1 studies. Finally, the challenges and opportunities for L1 mouse models are discussed.