Gene expression

Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Dou, Y. et al. Cell 121, 873–885 (2005)

Acetylation of histone 4 (H4) on K16 and methylation of K4 on H3 are independently associated with transcriptional activation, but evidence indicates that these two modifications often function in coordinated combinations. Dou et al. have now discovered that the H3 K4 methyltransferase MLL1 is part of a complex that contains, among other components, MOF, which specifically acetylates H4 K16. The histone methyltransferase and histone acetyltransferase activities of the complex were required for transcriptional activation on a chromatin template and an MLL1-target gene in vivo. So, the isolation of this complex provides a functional connection between the two histone modifications.

Cell fate

Delta–Notch signalling controls commitment to a secretory fate in the zebrafish intestine. Crosnier, C. et al. Development 132, 1093–1104 (2005)

Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. van Es, J. H. et al. Nature 435, 959–963 (2005)

Notch signals control the fate of immature progenitor cells in the intestine. Fre, S. et al. Nature 435, 964–968 (2005)

The first of these three papers reports an increase in the number of secretory cells at the expense of absorptive cells in the zebrafish gut in the absence of Delta–Notch signalling. The authors of the second and third papers also studied the intestine, but in mice. When van Es et al. blocked Delta–Notch signalling, this caused proliferative cells in the crypt to convert into differentiated goblet cells. Conversely, Fre et al. activated Notch signalling, which prevented secretory-cell differentiation and increased the population of progenitor cells.

Endocytosis

Protein kinase activity of phosphoinositide 3-kinase regulates β-adrenergic receptor endocytosis. Naga Prasad, S. V. et al. Nature Cell Biol. 10 July 2005 (10.1038/ncb1278)

These authors have identified the first protein target of phosphoinositide 3-kinase (PI3K) — a protein and lipid kinase, the lipid-kinase activity of which is known to be important in signalling. They have found that the cytoskeletal protein non-muscle tropomyosin is a substrate for the protein-kinase activity of PI3K, and that the PI3K-mediated phosphorylation of tropomyosin on Ser61 is essential for the agonist-dependent internalization of the β-adrenergic receptor.