Molecular biology of the leukaemia inhibitory factor gene

Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that has been identified and characterized in several laboratories by virtue of a number of different biological activities. LIF is encoded by a unique gene located at 11A1 in the mouse and at 22q12 in man. However, loci related to sequences in the 3' untranslated region of the mRNA have been detected and located elsewhere in the genome. The LIF gene from four mammalian species has been cloned and sequenced; the sequences are highly conserved within the coding regions and largely non-conserved within the non-coding regions. However, a number of non-coding segments displaying high interspecies similarity are evident; these are candidate control regions. Intriguingly, an exon corresponding to the 5' end of a variant LIF transcript in the mouse that encodes a potentially matrix-associated form of LIF is not conserved in the human, ovine and porcine genes. The promoter region of the LIF gene contains four well-conserved TATA elements, and two start sites of transcription have been identified. Three regions within the 5' flanking region have been identified as important for the function of the LIF promoter, including a candidate repressor sequence. The LIF gene is transcribed at only very low levels in normal tissues, but its expression can be increased by various stimuli.