No abstract

MLL is involved in the process of gene activity maintenance. It is shown that the amino-terminal region of MLL (MLLN) interacts with TAF-Ib/SET. In this study, using yeast two-hybrid assays, we have found that the acidic region of TAF-Ib is essential for its binding to MLLN. Pull-down assays using GST-MLLN demonstrated that TAF-Ib and histones interact with GST-MLLN. MLLN and TAF-Ib synergistically upregulated the transcription level of Hoxa9 and co-immunoprecipitated in chromatin containing the Hoxa9 promoter region. These results suggest that TAF-Ib plays an important role in MLL-mediated transcription and possibly chromatin maintenance.

No abstract

Because cardiomyocyte generation is limited, the turnover of cardiomyocytes in adult heart tissues is much debated. We report here that cardiac pacemaker cells can generate cardiomyocytes from fibroblasts in vitro. Sinoatrial node cells (SANCs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. Within a week, a number of fibroblast-like cells were observed to gather around SANCs, and these formed spontaneously beating clusters with cardiomyocyte structures. The clusters expressed genes and proteins that are characteristic of atrial cardiomyocytes. Pharmacological blocking of pacemaker currents inhibited generation of action potentials, and the spontaneous beating were ceased by physically destroying a few central cells. Inhibition of beating during culture also hampered the cluster formation. Moreover, purified guinea pig cardiac fibroblasts (GCFs) expressed cardiac-specific proteins in co-culture with SANCs or in SANC-preconditioned culture medium under electrical stimulation. These results indicate that SANCs can generate cardiomyocytes from cardiac fibroblasts through the influence of humoral factor(s) and electrophysiological activities followed by intracellular Ca2+ oscillations. This potential of SANCs to generate cardiomyocytes indicates a novel mechanism by which cardiomyocytes turns over in the vicinity of pacemaker cells and could be exploited in the development of strategies for cardiac regenerative therapy in adult hearts.