The ATAC acetyltransferase complex coordinates MAP kinases to regulate JNK target genes.
In response to extracellular cues, signal transduction activates downstream transcription factors like c-Jun to induce expression of target genes. We demonstrate that the ATAC (Ada two A containing) histone acetyltransferase (HAT) complex serves as a transcriptional cofactor for c-Jun at the Jun N-terminal kinase (JNK) target genes Jra and chickadee. ATAC subunits are required for c-Jun occupancy of these genes and for H4K16 acetylation at the Jra enhancer, promoter, and transcribed sequences. Under conditions of osmotic stress, ATAC colocalizes with c-Jun, recruits the upstream kinases Misshapen, MKK4, and JNK, and suppresses further activation of JNK. Relocalization of these MAPKs and suppression of JNK activation by ATAC are dependent on the CG10238 subunit of ATAC. Thus, ATAC governs the transcriptional response to MAP kinase signaling by serving as both a coactivator of transcription and as a suppressor of upstream signaling.
Suganuma
Tamaki
T
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Mushegian
Arcady
A
Swanson
Selene K
SK
Abmayr
Susan M
SM
Florens
Laurence
L
Washburn
Michael P
MP
Workman
Jerry L
JL
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D020935:MAP Kinase Signaling System; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009997:Osmotic Pressure; D017434:Protein Structure, Tertiary; D013312:Stress, Physiological; D013466:Sulfurtransferases / Q000737:chemistry / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C411875:MBIP protein, human; D009097:Multienzyme Complexes; D051548:Histone Acetyltransferases; D048031:JNK Mitogen-Activated Protein Kinases; D013466:Sulfurtransferases; C085585:molybdopterin synthase