Downregulation of Testis Specific Protein Y-encoded like 2 in neonatal heart development

Abstract

In mammals, cardiomyocytes cease to proliferate soon after birth and become terminally differentiated. As the regeneration ability of cardiomyocytes is limited, the heart function usually cannot fully restore after infraction or heart failure. It is important to understand the mechanisms for controlling proliferation and cell cycle exit in cardiomyocytes. Testis specific protein Y-encoded like 2 (TSPYL2) contains a nucleosome assembly protein (NAP) domain which is characteristic of the TSPY/ NAP/SET superfamily. Members in this superfamily are suggested to be involved in the regulation of DNA synthesis, proliferation and transcription through their effects on nucleosome remodelling. We isolated TSPYL2 cDNA and its mouse homologue Tspyl2 by cDNA library screening. Tspyl2 was specifically expressed in the heart, brain and testis. Semi-quantitative PCR revealed that Tspyl2 was detected in the mouse embryonic heart at E11. The expression increased to the highest level at birth and then started to decline. By immunohistochemistry and western blotting, a similar trend in protein expression was observed with the level below detection at two weeks after birth. Downregulation of Tspyl2 was also observed in C2C12 and H9c2 cell lines upon differentiation to myotubes. Based on the expression pattern and the domain structure, we hypothesize that Tspyl2 is involved in the terminal differentiation of cardiomyocytes. Further studies will be conducted on C2C12 and H9c2 to investigate the role of Tspyl2 in proliferation and differentiation. [This work was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU7176/01M).]