CBF alpha 3 (AML2) is induced by TGF-beta 1 to bind and activate the mousegermline ig a promoter

TGF-beta 1 directs class switching to IgA by splenic B cells and by the sur face IgM(+) B cell line, I.29 mu, by inducing germline (GL) Ig a transcript s. The promoter segment between -130 and +46, relative to the first initiat ion site for mouse GL a transcripts, is sufficient for expression and TGF-b eta 1 inducibility of a reporter gene in B cell lines. Within this segment resides a TGF-beta 1-responsive element (T beta RE) that is required for in duction of the promoter by TGF-beta 1 and, when multimerized, is sufficient to transfer TGF-beta 1 inducibility to another promoter. In this report we show that a TGF-beta 1-inducible complex binds the T beta RE and contains the transcription factor core-binding factor (CBF; also known as acute myel oid leukemia, AML), Although all three CBF alpha family members activate th e GL alpha promoter, only CBF alpha 3 (AML-2) is induced by TGF-beta 1 in s plenic B and I.29 mu cells. The T beta RE contains two CBF binding sites. M utation of both sites reduces but does not eliminate induction of the GL a promoter by TGF-beta 1 or by overexpression of CBF, possibly due to the pre sence of an additional CBF site in the promoter. In addition, the T beta RE contains two copies of another sequence motif. Mutation of these motifs el iminates TGF-beta 1 induction of the GL a promoter. Together the data indic ate that TGF-beta 1 induction of the a promoter involves induction of CBF a lpha 3, which binds to the T beta RE of the promoter along with one or more proteins.