title: PARP-14 binds specific DNA sequences to promote Th2 cell gene expression.
abstract: PARP-14, a member of the poly ADP-ribose polymerase super family, promotes T helper cell 2 (Th2) differentiation by regulating interleukin-4 (IL-4) and STAT6-dependent transcription. Yet, whether PARP-14 globally impacts gene regulation has not been determined. In this report, using an RNA pol II ChIP-seq approach, we identify genes in Th2 cells that are regulated by PARP-14, and either dependent or independent of ADP-ribosyltransferase catalytic activity. Our data demonstrate that PARP-14 enhances the expression of Th2 genes as it represses the expression of Th1-associated genes. Among the relevant targets are Signal Transducer and Activator of Transcription genes required for polarizing Th1 and Th2 cells. To define a mechanism for PARP-14 function, we use an informatics approach to identify putative PARP-14 DNA binding sites. Two putative PARP-14 binding motifs are identified in multiple Th2 cytokine genes, and we demonstrate that PARP-14 interacts with each motif using in vitro binding assays. Taken together our results indicate that PARP-14 is an important factor for T helper cell differentiation and it binds to specific DNA sequences to mediate its function.
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Riley
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; School of Informatics, Indiana University-Purdue University, Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Byunghee
authors.initials: B
authors.lastname: Koh
authors.affiliation: School of Informatics, Indiana University-Purdue University, Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Narayanan B
authors.initials: NB
authors.lastname: Perumal
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Shreevrat
authors.initials: S
authors.lastname: Goenka
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D004247:DNA; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases