PARP-14 Functions as a Transcriptional Switch for Stat6-dependent Gene Activation

• DOI: 10.1074/jbc.m110.157768
• Publication Date: 2010-11-17T01:24:37Z
• Authors: Purvi Mehrotra; Jonathan P. Riley; Ravi Patel; Fang Li; Le'erin Voss; Shreevrat Goenka
• Keywords: Mice, Knockout; 0301 basic medicine; Transcription, Genetic; Histone Deacetylase 2; T-Lymphocytes, Helper-Inducer; Histone Deacetylases; Cell Line; Repressor Proteins; Mice; 03 medical and health sciences; Animals; Interleukin-4; Poly(ADP-ribose) Polymerases; Promoter Regions, Genetic; STAT6 Transcription Factor

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.