%0 Journal Article %1 Zhao20141595 %A Zhao, Bo %A Barrera, Luis A. %A Ersing, Ina %A Willox, Bradford %A Schmidt, Stefanie C.S. %A Greenfeld, Hannah %A Zhou, Hufeng %A Mollo, Sarah B. %A Shi, Tommy T. %A Takasaki, Kaoru %A Jiang, Sizun %A Cahir-McFarland, Ellen %A Kellis, Manolis %A Bulyk, Martha L. %A Kieff, Elliott %A Gewurz, Benjamin E. %D 2014 %J Cell Reports %K myown %N 5 %P 1595 - 1606 %R http://dx.doi.org/10.1016/j.celrep.2014.07.037 %T The NF-κB Genomic Landscape in Lymphoblastoid B Cells %U http://www.sciencedirect.com/science/article/pii/S2211124714006214 %V 8 %X Summary The nuclear factor κB (NF-κΒ) subunits RelA, RelB, cRel, p50, and p52 are each critical for B cell development and function. To systematically characterize their responses to canonical and noncanonical NF-κB pathway activity, we performed chromatin immunoprecipitation followed by high-throughput \DNA\ sequencing (ChIP-seq) analysis in lymphoblastoid B cell lines (LCLs). We found a complex NF-κB-binding landscape, which did not readily reflect the two NF-κB pathway paradigms. Instead, 10 subunit-binding patterns were observed at promoters and 11 at enhancers. Nearly one-third of NF-κB-binding sites lacked κB motifs and were instead enriched for alternative motifs. The oncogenic forkhead box protein \FOXM1\ co-occupied nearly half of NF-κB-binding sites and was identified in protein complexes with NF-κB on DNA. \FOXM1\ knockdown decreased NF-κB target gene expression and ultimately induced apoptosis, highlighting \FOXM1\ as a synthetic lethal target in B cell malignancy. These studies provide a resource for understanding mechanisms that underlie NF-κB nuclear activity and highlight opportunities for selective NF-κB blockade.

@article{Zhao20141595, abstract = {Summary The nuclear factor κB (NF-κΒ) subunits RelA, RelB, cRel, p50, and p52 are each critical for B cell development and function. To systematically characterize their responses to canonical and noncanonical NF-κB pathway activity, we performed chromatin immunoprecipitation followed by high-throughput \{DNA\} sequencing (ChIP-seq) analysis in lymphoblastoid B cell lines (LCLs). We found a complex NF-κB-binding landscape, which did not readily reflect the two NF-κB pathway paradigms. Instead, 10 subunit-binding patterns were observed at promoters and 11 at enhancers. Nearly one-third of NF-κB-binding sites lacked κB motifs and were instead enriched for alternative motifs. The oncogenic forkhead box protein \{FOXM1\} co-occupied nearly half of NF-κB-binding sites and was identified in protein complexes with NF-κB on DNA. \{FOXM1\} knockdown decreased NF-κB target gene expression and ultimately induced apoptosis, highlighting \{FOXM1\} as a synthetic lethal target in B cell malignancy. These studies provide a resource for understanding mechanisms that underlie NF-κB nuclear activity and highlight opportunities for selective NF-κB blockade. }, added-at = {2016-11-16T00:47:29.000+0100}, author = {Zhao, Bo and Barrera, Luis A. and Ersing, Ina and Willox, Bradford and Schmidt, Stefanie C.S. and Greenfeld, Hannah and Zhou, Hufeng and Mollo, Sarah B. and Shi, Tommy T. and Takasaki, Kaoru and Jiang, Sizun and Cahir-McFarland, Ellen and Kellis, Manolis and Bulyk, Martha L. and Kieff, Elliott and Gewurz, Benjamin E.}, biburl = {https://www.bibsonomy.org/bibtex/240aba77c17dc72db88ce51dab483cbb6/bgewurz}, doi = {http://dx.doi.org/10.1016/j.celrep.2014.07.037}, interhash = {b89e33dc2756763e5fdbb173e6085b7c}, intrahash = {40aba77c17dc72db88ce51dab483cbb6}, issn = {2211-1247}, journal = {Cell Reports }, keywords = {myown}, number = 5, pages = {1595 - 1606}, timestamp = {2016-11-16T00:48:20.000+0100}, title = {The NF-κB Genomic Landscape in Lymphoblastoid B Cells }, url = {http://www.sciencedirect.com/science/article/pii/S2211124714006214}, volume = 8, year = 2014 }