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Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions...
Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and...
An unexpected role for a Mediator subunit, MED12, in resistance to multiple anticancer agents is revealed by Huang et al. Loss of MED12 confers drug resistance by activating transforming growth factor β (TGF-β) signaling. Inhibition of the TGF-β pathway resensitizes cells to therapeutic drugs, suggesting a new combinatorial cancer treatment.
TGF-β ligands induce phosphorylation of receptor-activated Smads at both the C-terminal tail and the linker region. Two papers from Massagué and colleagues (Alarcón et al., 2009; Gao et al., 2009) reveal a dual role for this linker phosphorylation, which is required for activation of Smads and for their degradation.
DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser287 phosphorylation is a major locus of G2/M checkpoint control, although several checkpoint-independent kinases can phosphorylate this site. We reported...
In this issue of Cell, Lin et al. (2006) answer one of the long-standing questions in the TGFβ field by identifying a phosphatase, PPM1A, that directly dephosphorylates Smad2 and Smad3 to limit their activation.
Axon outgrowth is the first step in the formation of neuronal connections, but the pathways that regulate axon extension are still poorly understood. We find that mice deficient in calcineurin-NFAT signaling have dramatic defects in axonal outgrowth, yet have little or no defect in neuronal differentiation or survival. In vitro, sensory and commissural neurons lacking calcineurin function or NFATc2,...
Olfactory neurons expressing a given odorant receptor project with precision to 2 of the 1800 glomeruli within the olfactory bulb to create a topographic map of odor quality. We demonstrate that deletions or nonsense mutations in the P2 odorant receptor gene cause the axons of these cells to wander rather than converge on a specific glomerulus. Receptor substitution experiments that replace the P2...
Spinal muscular atrophy (SMA), one of the most common fatal autosomal recessive diseases, is characterized by degeneration of motor neurons and muscular atrophy. The SMA disease gene, termed Survival of Motor Neurons (SMN), is deleted or mutated in over 98% of SMA patients. The function of the SMN protein is unknown. We found that SMN is tightly associated with a novel protein, SIP1, and together...
Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRNP A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-mediated...
We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes...
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