ATAC and Mediator coactivators form a stable complex and regulate a set of non-coding RNA genes.

The Ada-Two-A-containing (ATAC) histone acetyltransferase and Mediator coactivator complexes regulate independent and distinct steps during transcription initiation and elongation. Here, we report the identification of a new stable molecular assembly formed between the ATAC and Mediator complexes in mouse embryonic stem cells. Moreover, we identify leucine zipper motif-containing protein 1 as a subunit of this meta-coactivator complex (MECO). Finally, we demonstrate that the MECO regulates a subset of RNA polymerase II-transcribed non-coding RNA genes. Our findings establish that transcription coactivator complexes can form stable subcomplexes to facilitate their combined actions on specific target genes.