LINE‐1 influences cellular differentiation via mechanisms that involve Ahr signaling

Long Interspersed Nuclear Element‐1 (LINE‐1) or L1 is a mobile element in the mammalian genome that propagates via a “copy‐and‐paste” mechanism using reverse transcriptase and RNA intermediates. Although molecular mechanisms of L1 regulation remain elusive, increased L1 expression is observed in developing mammalian embryos, transformed cells, and atherosclerotic plaques. These phenotypes are all representative of undifferentiated states and therefore, L1 may participate in the regulation of cellular differentiation. The present studies were conducted to evaluate the impact of stress‐activated L1 expression on cellular differentiation in mouse vascular smooth muscle cells (mVSMC). Transient ectopic expression of L1 in mVSMCs) affected the levels of several differentiation markers including, calponin and smooth muscle actin. Stable L1 expression in mVSMCs increases growth rates and promotes resistance to apoptosis mediated by geneticin, a translational inhibitor. Genetic and pharmacological experiments showed that aryl hydrocarbon receptor (Ahr) was involved in the activation of endogenous L1 by environmental stress and the transactivation of a mouse L1 promoter construct (L1Md‐A5). These data indicate that L1 activation in mammalian cells affects cellular differentiation status and implicate Ahr as a molecular determinant of L1 inducibility.