A POSSIBLE INVOLVEMENT OF TIF1-ALPHA AND TIF1-BETA IN THE EPIGENETIC CONTROL OF TRANSCRIPTION BY NUCLEAR RECEPTORS

Nuclear receptors (NRs) are ligand-inducible transcription factors tha t mediate complex effects on development, differentiation and homeosta sis. They regulate the transcription of their target genes through bin ding to cognate DNA sequences as homodimers or heterodimers, The molec ular mechanisms underlying transcriptional activation by NRs are still poorly understood, although intermediary factors (mediators) appear t o be involved in mediating the transactivation functions of NRs, TIF1 has been identified previously as a protein that interacts specificall y with the ligand binding domain of several nuclear receptors, both in yeast and in vitro. The characteristics of these interactions have le d us to suggest that TIF1 might be a mediator of the NR ligand-inducib le activation function AF-2, Using a two-hybrid screening in yeast, we have now identified two TLFP-binding proteins, mHP1 alpha and mMOD1, that are mouse homologues of the Drosophila heterochromatinic protein 1. Using mHP1 alpha as a bait in a second two-hybrid screening, we hav e isolated cDNAs encoding proteins that are also very likely to be inv olved in chromatin structure and function, as well as a protein struct urally and functionally related to TIF1 (renamed TLF1 alpha), which wa s named TIF1 beta. Here we discuss how the function of members of the TIF1 family in the control of transcription could be exerted at the le vel of the structure of the chromatin template.