This is obviously not the case. Interestingly, also maternally and paternally expressed genes are not regulated by distinct sets of transcription factor families. In general, a few genes, i.e. UBE3A, KLF14, BLCAP, NAP1L5, NNAT, and GNAS, show an overproportional enrichment of distinct transcription factor binding sites. Interestingly, these genes possess rather diverse functions. For example, UBE3A seems to act in neuronal development, whereas GNAS acts mostly in endocrinal pathways. Although imprinted genes appear to be regulated by similar sets of transcription factors in mouse and human, it is difficult to identify a typical transcription factor that regulates imprinted genes. The most prominent factor appears to be SP1. This rather ubiquitous factor might be responsible for the broad tissue spectrum of imprinted genes. On the other hand SP1 deficiency is to some extent associated with placental defects and impaired ossification, that are typical features of defects in imprinting. Varrault and co-workers have recently identified a network of coregulated imprinted genes involving the genes Plagl1, Gtl2, H19, Mest, Dlk1, Peg3, Grb10, Igf2, Igf2r, Dcn, Gnas, Gatm, Ndn, Cdkn1c and Slc33a4. According to Fig. 6, E12 regulates four genes from this list ; SP1 regulates three genes as well as AACTTT_UNKNOWN. We suggest these three transcription factors as candidates that may be responsible for the coregulation of this imprinting network. Berg and colleagues recently analyzed the expression levels of ten of these genes in mouse long-term repopulating hematopoietic stem cells and in representative differentiated lineages. NSC 136476 cost Intriguingly, they found that most of the genes were severely down regulated in differentiated cells. They noticed that their study is the first one that connected imprinted genes that are known to be associated with embryonic and early postnatal growth to the regulation of somatic stem cells. Consequently, they suggested that the balancing forces of growth-promoting paternally expressed genes and of growth-limiting maternally expressed genes may as well play a role in keeping stem cells in the delicate balance of pluripotency. Along these lines, but in the opposite direction, our above finding that the global transcription factors E12 and SP1 play key roles in the regulation of imprinted genes fits to their wellknown role in cell differentiation processes. Growth hormone plays a pivotal role in multiple physiological processes in mammals. It is essential for somatic growth, is a key contributor to normal tissue differentiation and repair, and is an important regulator of intermediary metabolism. GH also has been implicated in aging and in the development of certain cancers, implying that in the adult its activity must be limited in scope and duration to maintain physiological homeostasis. Thus, its positive physiological effects while limiting its negative impact on human disease. Like other members of the cytokine receptor family, upon ligand binding the GH receptor engages and stimulates the Jak – Stat signaling pathway. GH binding induces the receptor-associated tyrosine kinase, Jak2 to phosphorylate tyrosine residues on the intracellular part of the receptor, leading to the recruitment of several Stats, as well as other signaling molecules. Stats comprise a group of seven related proteins in mammals, with the first members being characterized as signaling agents for interferons a/b and c. Subsequent studies have broadened the biological importance of this protein family as critical components of multiple physiological and patho-physiological processes. Stats are typically found in the cytoplasm of responsive cells prior to hormone or cytokine stimulation.