Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA

Proteins containing AT hooks bind A/T-rich DNA through a nine-amino-acid mo tif and are thought to co-regulate transcription by modifying the architect ure of DNA, thereby enhancing the accessibility of promoters to transcripti on factors(1,2). Here we describe AKNA, a human AT-hook protein that direct ly binds the A/T-rich regulatory elements of the promoters of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression. Consistent wit h its function, AKNA is a nuclear protein that contains multiple PEST prote in-cleavage motifs, which are common in regulatory proteins with high turno ver rates(3). AKNA is mainly expressed by B and T lymphocytes, natural kill er cells and dendritic cells. During B-lymphocyte differentiation, AKNA is mainly expressed by germinal centre B lymphocytes, a stage in which recepto r and ligand interactions are crucial for B-lymphocyte maturation(4-12). Ou r findings show that an AT-hook molecule can coordinately regulate the expr ession of a key receptor and its ligand, and point towards a molecular mech anism that explains homotypic cell interactions.