Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling Export

@article{citeulike:6032670, abstract = {Protein-DNA interactions (PDIs) mediate a broad range of functions essential for cellular differentiation, function, and survival. However, it is still a daunting task to comprehensively identify and profile sequence-specific PDIs in complex genomes. Here, we have used a combined bioinformatics and protein microarray-based strategy to systematically characterize the human protein-DNA interactome. We identified 17,718 PDIs between 460 DNA motifs predicted to regulate transcription and 4,191 human proteins of various functional classes. Among them, we recovered many known PDIs for transcription factors (TFs). We identified a large number of unanticipated PDIs for known TFs, as well as for previously uncharacterized TFs. We also found that over three hundred unconventional DNA-binding proteins (uDBPs)which include RNA-binding proteins, mitochondrial proteins, and protein kinasesshowed sequence-specific PDIs. One such uDBP, ERK2, acts as a transcriptional repressor for interferon gamma-induced genes, suggesting important biological roles for such proteins.}, author = {Hu, Shaohui and Xie, Zhi and Onishi, Akishi and Yu, Xueping and Jiang, Lizhi and Lin, Jimmy and Rho, Hee-sool and Woodard, Crystal and Wang, Hong and Jeong, Jun-Seop and Long, Shunyou and He, Xiaofei and Wade, Herschel and Blackshaw, Seth and Qian, Jiang and Zhu, Heng}, citeulike-article-id = {6032670}, citeulike-linkout-0 = {http://www.cell.com//abstract/S0092-8674(09)01111-8}, comment = {Used synthetic nucleotides representing 460 conserved and 'sequence-divergent' (i.e. different) motifs to probe a human protein array containing not only transcription factors and other nucleic acid binding proteins but many proteins with other functions and with no link to DNA binding (total 4191 proteins). "Many TFs with highly divergent protein sequences bound to highly similar or even identical target DNA sequences" This implies a) that similar TFs don't bind similar targets b) unrelated TFs can converge on same recognition sequence. Many of the proteins with novel roles in DNA-binding do so quite specifically (e.g. less than 30 oligos). ERK2 represses several interferon-responsive genes and in at least one example, binds to same site as a positive regulator TF. }, day = {30}, keywords = {cis-regulatory\_element, gene\_regulation, genomics, interactions, transcription\_factors, transcriptional\_repressor}, month = {October}, number = {3}, pages = {610--622}, posted-at = {2009-10-30 11:28:30}, priority = {0}, title = {Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling}, url = {http://www.cell.com//abstract/S0092-8674(09)01111-8}, volume = {139}, year = {2009} }

TY - JOUR ID - citeulike:6032670 L3 - citeulike-article-id:6032670 N2 - Protein-DNA interactions (PDIs) mediate a broad range of functions essential for cellular differentiation, function, and survival. However, it is still a daunting task to comprehensively identify and profile sequence-specific PDIs in complex genomes. Here, we have used a combined bioinformatics and protein microarray-based strategy to systematically characterize the human protein-DNA interactome. We identified 17,718 PDIs between 460 DNA motifs predicted to regulate transcription and 4,191 human proteins of various functional classes. Among them, we recovered many known PDIs for transcription factors (TFs). We identified a large number of unanticipated PDIs for known TFs, as well as for previously uncharacterized TFs. We also found that over three hundred unconventional DNA-binding proteins (uDBPs)which include RNA-binding proteins, mitochondrial proteins, and protein kinasesshowed sequence-specific PDIs. One such uDBP, ERK2, acts as a transcriptional repressor for interferon gamma-induced genes, suggesting important biological roles for such proteins. IS - 3 EP - 622 TI - Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling VL - 139 SP - 610 KW - cis-regulatory_element KW - gene_regulation KW - genomics KW - interactions KW - transcription_factors KW - transcriptional_repressor N1 - Used synthetic nucleotides representing 460 conserved and 'sequence-divergent' (i.e. different) motifs to probe a human protein array containing not only transcription factors and other nucleic acid binding proteins but many proteins with other functions and with no link to DNA binding (total 4191 proteins). "Many TFs with highly divergent protein sequences bound to highly similar or even identical target DNA sequences" This implies a) that similar TFs don't bind similar targets b) unrelated TFs can converge on same recognition sequence. Many of the proteins with novel roles in DNA-binding do so quite specifically (e.g. less than 30 oligos). ERK2 represses several interferon-responsive genes and in at least one example, binds to same site as a positive regulator TF. AU - Hu, Shaohui AU - Xie, Zhi AU - Onishi, Akishi AU - Yu, Xueping AU - Jiang, Lizhi AU - Lin, Jimmy AU - Rho, Hee-sool AU - Woodard, Crystal AU - Wang, Hong AU - Jeong, Jun-Seop AU - Long, Shunyou AU - He, Xiaofei AU - Wade, Herschel AU - Blackshaw, Seth AU - Qian, Jiang AU - Zhu, Heng PY - 2009/10/30/ UR - http://www.cell.com//abstract/S0092-8674(09)01111-8 ER -