Isolation and characterization of a human collagen α 1(I)-like gene from a cosmid library

We have isolated a human collagen α1(I)-like gene from a cosmid library. The clone which contains 37kb of human DNA has been shown to contain this gene by DNA sequencing, hybrid arrest and hybrid selection assays and Northern blot hybridizations. The collagen gene sequence extends through most of the cloned DNA and must, therefore, be at least 35kb in length. © 1982 IRL Press Limited.link_to_OA_fulltex

TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis

The t(12;21)(p13;q22) is identified by routine cytogenetics in less than 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. This translocation encodes a TEL/AML-1 chimeric product comprising the helix-loop-helix domain of TEL, a member of the ETS-like family of transcription factors, fused to AML-1, the DNA-binding subunit of the AML-1/CBFβ transcription factor complex. Both TEL and AML-1 are involved in several myeloid leukemia-associated translocations with AML-1/CBFβ being altered in 20-30% of de novo acute myeloid leukemia (AML) cases. We now demonstrate that a TEL/AML1 chimeric transcript encoded by a cryptic t(12;21) is observed in 22% of pediatric ALL, making it the most common genetic lesion in these patients. Moreover, TEL/AML1 expression defined a distinct subgroup of patients characterized by an age between 1 and 10 years, B lineage immunophenotype, nonhyperdiploid DNA content and an excellent prognosis. These data demonstrate that molecular diagnostic approaches are invaluable in identifying clinically distinct subgroups, and that the AML1/CBFβ transcription complex is the most frequent target of chromosomal rearrangements in human leukemia.link_to_subscribed_fulltex

Binding of nuclear factor kappa B to non-canonical consensus sites reveals its multimodal role during the early inflammatory response

Mammalian cells have developed intricate mechanisms to interpret, integrate, and respond to extra-cellular stimuli. For example, tumor necrosis factor (TNF) rapidly activates proinflammatory genes, but our understanding of how this occurs against the ongoing transcriptional program of the cell is far from complete. We monitor the early phase of this cascade at high spatio-temporal resolution in TNFα-stimulated human endothelial cells. The main driver of the response, NF-κB, hijacks the regulatory machinery by binding active enhancers already-interacting with gene promoters. Notably, a large fraction of these enhancers do not encode the canonical NF-κB recognition motif. Using a combination of genomics tools we find that site selection is a key determinant of NF-κΒ participation in both transcriptional activation and repression, and we exemplify the repressive NF-κΒ function via its synergy with the JDP2 co-repressor. Finally, detailed analysis of a 3-Mbp locus using both targeted chromatin conformation capture and genome editing uncovers how newly-introduced NF-κΒ exploits pre-existing chromatin looping to exert its multimodal role. This work dissects the involvement of topology in the function of cis-regulatory elements during acute transcriptional responses, where primary sequence and higher-order structure constitute the regulatory context leading to either gene activation or repression