TIPT, a male germ cell-specific partner of TRF2, is chromatin-associated and interacts with HP1

The differentiation process of spermatogenesis is based on a finely timed program of transcriptional regulation and chromatin remodeling. Male germ cells utilize specialized transcription complexes, which display specific differences in the components of the general transcription machinery. The TATA-binding protein (TBP)-related protein 2 (TRF2) is essential for progression in spermiogenesis and for the structuring of the chromocenter, an heterochromatic structure unique of round spermatids. To decipher the molecular pathways of TRF2 action, we have searched for TRF2 partners in male germ cells. We have isolated TIPT ( TRF2 interacting protein in testis), a relatively small protein that associates with TRF2 with affinity comparable to TFIIA. TIPT is uniquely expressed in testis, with a developmental pattern that temporally parallels the one of TRF2. Importantly, TIPT interacts also with HP1 proteins, thereby establishing an intriguing link between transcription and chromatin condensation. Association of TIPT with either TRF2 or HP1 occurs through the C-terminal domain in a mutually exclusive manner. These findings indicate that TIPT could contribute to the precise timing of the molecular events in male germ cells, specifically by linking transcription to chromatin remodeling in round spermatids.