Human TFIID contains the TATA-binding protein (TBP) and several TBP-associated factors (hTAFs) that have been shown to play important roles, within TFIID, both in core promoter recognition and as coactivators. Here we show that the human TAF(II)43 (TAF8) is an integral component of a functional TFIID and an apparent ortholog to the recently reported mouse TBN, which is essential for early embryonic mouse developmental events. Significantly, we also show that TAF8 is dramatically induced and sequestered within TFIID upon differentiation of 3T3-L1 preadipocytes to adipocytes, whereas the expression of all other TAFs tested is slightly reduced. Moreover, when ectopically expressed, the histone fold domain of TAF8 acts as a dominant-negative mutant and selectively inhibits 3T3-L1 adipogenic differentiation. Furthermore TAF8 acts as a positive regulator of adipogenesis and reverses the inhibitory effect of its histone fold. These data suggest a selective role for TAF8 in a specific cell differentiation process(es).