Loss of function mutations in SALL4 cause Okihiro syndrome, an autosomal dominant disorder characterised by radial ray malformations associated with Duane anomaly. In zebrafish and mouse Sa114 interacts with TBX5 during limb and heart development and plays a crucial role for embryonic stem (ES) cell pluripotency. Here we report the nuclear interaction of murine Sa114 with Cyclin D1, one of the main regulators of G, to S phase transition in cell cycle, verified by yeast two-hybrid assay, co-immunoprecipitation and intracellular co-localisation. Furthermore, using luciferase reporter gene assays we demonstrate that Sa114 operates as a transcriptional repressor located to heterochromatin and that this activity is modulated by Cyclin D1. (c) 2007 Elsevier Inc. All rights reserved.