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Cell fate decisions occur through the switch-like, irreversible activation of fate-specifying genes. These activation events are often assumed to be tightly coupled to changes in upstream transcription factors, but could also be constrained by cis-epigenetic mechanisms at individual gene loci. Here, we studied the activation of Bcl11b, which controls T-cell fate commitment. To disentangle cis and trans effects, we generated mice where two Bcl11b copies are tagged with distinguishable fluorescent proteins. Quantitative live microscopy of progenitors from these mice revealed that Bcl11b turned on after a stochastic delay averaging multiple days, which varied not only between cells but also between Bcl11b alleles within the same cell. Genetic perturbations, together with mathematical modeling, showed that a distal enhancer controls the rate of epigenetic activation, while a parallel Notch-dependent trans-acting step stimulates expression from activated loci. These results show that developmental fate transitions can be controlled by stochastic cis-acting events on individual loci.
Pubmed ID: 30457103 RIS Download
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It is the distribution arm of their academic laboratory. They operate on a cost-recovery mechanism in order to make the resources generated in their laboratory available to the academic scientific community. While clones and screening services are widely available, library arrays are primarily available to researchers with a scientific need to analyze most clones in the library. This site contains information on currently available BAC and PAC genomic DNA libraries, BAC Clones, PAC Clones, Fosmid Clones, cDNA collections, high-density colony hybridization filters, and BAC and PAC cloning vectors. Protocols used in our laboratory for the hybridization-based screening of colony filters, purification of BAC and PAC DNA, and end-sequencing methodologies, are also provided. BPRC does not list clones, for two reasons: 1)most clones have not been characterized and lack specific data. 2)all clones are part of libraries and all clones from a particular library share common characteristics. Hence, to find out if BPRC has a particular clone, one needs either use Automatic Clone Validation or else find out if the clone is compatible with the range of clone names for a corresponding clone library. Typically (although not always), clone names are derived from the library name. BPRC uses the NCBI-recommended clone nomenclature & library nomenclature. Most arrayed libraries are available in frozen microtiter dish format to academic and non-academic users provided that there is a scientific need for complete-library access. (for instance to annotate, modify or analyze all BAC clones as part of a genome project).
View all literature mentionsIt is the distribution arm of their academic laboratory. They operate on a cost-recovery mechanism in order to make the resources generated in their laboratory available to the academic scientific community. While clones and screening services are widely available, library arrays are primarily available to researchers with a scientific need to analyze most clones in the library. This site contains information on currently available BAC and PAC genomic DNA libraries, BAC Clones, PAC Clones, Fosmid Clones, cDNA collections, high-density colony hybridization filters, and BAC and PAC cloning vectors. Protocols used in our laboratory for the hybridization-based screening of colony filters, purification of BAC and PAC DNA, and end-sequencing methodologies, are also provided. BPRC does not list clones, for two reasons: 1)most clones have not been characterized and lack specific data. 2)all clones are part of libraries and all clones from a particular library share common characteristics. Hence, to find out if BPRC has a particular clone, one needs either use Automatic Clone Validation or else find out if the clone is compatible with the range of clone names for a corresponding clone library. Typically (although not always), clone names are derived from the library name. BPRC uses the NCBI-recommended clone nomenclature & library nomenclature. Most arrayed libraries are available in frozen microtiter dish format to academic and non-academic users provided that there is a scientific need for complete-library access. (for instance to annotate, modify or analyze all BAC clones as part of a genome project).
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