Summary In animals, many cells reach their destinations by migrating towards higher concentrations of an attractant. However, the nature, generation and interpretation of attractant gradients are poorly understood. Using a GFP fusion and a signaling sensor, we analyzed the distribution of the attractant chemokine Sdf1 during migration of the zebrafish posterior lateral line primordium, a cohort of about 200 cells that migrates over a stripe of cells uniformly expressing sdf1. We find that a small fraction of the total Sdf1 pool is available to signal and induces a linear Sdf1-signaling gradient across the primordium. This signaling gradient is initiated at the rear of the primordium, equilibrates across the primordium within 200 minutes, and operates near steady-state. The rear of the primordium generates this gradient through continuous sequestration of Sdf1 protein by the alternate Sdf1-receptor Cxcr7. Modeling shows that this is a physically plausible scenario.

Acetylation of the histone tails, catalyzed by histone acetyltransferases (HATs), is a well-studied process that contributes to transcriptionally active chromatin states. Here we report the characterization of a novel mammalian HAT complex, which contains the two acetyltransferases GCN5 and ATAC2 as well as other proteins linked to chromatin metabolism. This multisubunit complex has a similar but distinct subunit composition to that of the Drosophila ADA2A-containing complex (ATAC). Recombinant ATAC2 has a weak HAT activity directed to histone H4. Moreover, depletion of ATAC2 results in the disassembly of the complex, indicating that ATAC2 not only carries out an enzymatic function but also plays an architectural role in the stability of mammalian ATAC. By targeted disruption of the Atac2 locus in mice, we demonstrate for the first time the essential role of the ATAC complex in mammalian development, histone acetylation, cell cycle progression, and prevention of apoptosis during embryogenesis.Chromatin is a dynamic nucleoprotein filament that undergoes dynamic chemical and conformational changes throughout the eukaryotic cell cycle (3). The compaction state of chromatin has a direct impact on transcription, replication, and DNA repair and recombination, all of which are nuclear processes that require DNA as a template. Successful execution of these processes requires modification of the nucleosome architecture by a variety of cellular machineries, which include chromatin-remodeling complexes as well as enzymatic complexes involved in posttranslational modifications of the histone tails (26,50).Histone acetyltransferases (HATs) are the key enzymes responsible for the acetylation of the histone tails. One of the most-studied HATs is GCN5, a protein conserved from Saccharomyces cerevisiae to humans (9, 51). This protein carries two conserved domains: an acetyltransferase domain required for its catalytic activity and a bromodomain that binds acetylated lysine residues (8,40,41). Recombinant yeast Gcn5 preferentially modifies histone H3 K14 and histone H4 K8 and K16 (28). However, the incorporation of yeast Gcn5 into native multisubunit complexes expands its substrate specificity, enabling it to acetylate histone H3 K9 and K18 in addition to K14 (19). In vivo studies of metazoans show a similar yet not identical substrate specificity for GCN5. For instance, polytene chromosomes isolated from gcn5 mutant fly larvae show reduced levels of acetylated H3 K9 and K14, as well as H4 K5 and K12 (10, 12). In addition, chicken DT40 cells devoid of GCN5 selectively display reduced levels of acetylated histone H3 K9 (25).To date, mammalian GCN5 has been identified in SPT3-TAF9-GCN5 acetyltransferase (STAGA) and the TATA-binding protein (TBP)-free TAF complex (TFTC), two multisubunit complexes that facilitate transcription from chromatin templates by acetylating histones H3 and H4 (7, 32, 33). These two highly similar complexes contain a subset of the TBPassociated factors (TAFs) found in TFIID as well as orthologues of the ye...

Chemokines are a group of small, secreted molecules that signal through G protein-coupled receptors to promote cell survival and proliferation and to provide directional guidance to migrating cells. CXCL12 is one of the most evolutionary conserved chemokines and signals through the chemokine receptor CXCR4 to guide cell migration during embryogenesis, immune cell trafficking and cancer metastasis. Here and in the accompanying poster, we provide an overview of chemokine signaling, focusing on CXCL12, and we highlight some of the different chemokine-dependent strategies used to guide migrating cells.

A popular theory in the stem cell field is that 'regeneration recapitulates development', or that adult stem cells function similarly to embryonic ones. In a recent Nature article, Lepper et al. questioned this approach, highlighting the differences in requirements for Pax7 during myogenesis for embryonic, juvenile and adult muscle.