title: PARP-14 functions as a transcriptional switch for Stat6-dependent gene activation.
abstract: A subset of poly ADP-ribose polymerases (PARP) that also contain macro domains regulate transcription. One such macro PARP, PARP-14 alters interleukin 4 (IL-4) and Stat6-dependent transcription. Stat6, activated by IL-4 plays an important role in T helper cell immunity and B cell responses. Here we define the mechanism by which PARP-14 regulates Stat6-activated transcription. Under non-stimulating conditions, PARP-14 recruits HDAC 2 and 3 to IL-4 responsive promoters. In the presence of IL-4, PARP-14 promotes efficient binding of Stat6 to its target genes. Moreover, HDAC 2 and 3 are released from the promoter with an IL-4 signal, this is aided by the ADP-ribosylation of the HDACs by PARP-14. The HDACs and PARP-14 get replaced by coactivators containing HAT activity. Based on these observations we put forth a mechanism in which PARP-14 functions as a transcriptional switch for Stat6-dependent gene induction. Thus, in the absence of a signal PARP-14 acts as a transcriptional repressor by recruiting HDACs. In contrast, in the presence of IL-4 the catalytic activity of PARP-14 facilitates Stat6 binding to the promoter, and release of HDACs so as to activate transcription.
authors.affiliation: Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Riley
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Le'erin
authors.initials: L
authors.lastname: Voss
authors.forename: Shreevrat
authors.initials: S
authors.lastname: Goenka
mesh_terms: D000818:Animals; D002460:Cell Line; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000099186:Histone Deacetylase 3
chemical_list: D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D015847:Interleukin-4; D011065:Poly(ADP-ribose) Polymerases; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; D000099186:Histone Deacetylase 3; C494100:Stat6 protein, mouse; C522628:Parp14 protein, mouse; C533424:Hdac2 protein, mouse