TAF-I, one of histone chaperones, consists of two subtypes, TAF-I alpha and TAF-I beta. The histone chaperone activity of TAF-I is regulated by dimer patterns of these subtypes. TAF-I beta is expressed ubiquitously, while the expression level of TAF-I alpha with less activity than TAF-I beta differs among cell types. It is, therefore, assumed that the expression level of TAF-I alpha in a cell is important for the TAF-I activity level. Here, we found that TAF-I alpha and TAF-I beta genes are under the control of distinct promoters. Reporter assays and gel shift assays demonstrated that Sp1 binds to three regions in the TAF-I alpha promoter and two or all mutaions of the three Sp1 binding regions reduced the TAF-I alpha promoter activity. ChIP assays demonstrated that Sp1 binds to the TAF-I alpha promoter in vivo. Furthermore, the expression level of TAF-I alpha mRNA was reduced by knockdown of Sp1 using siRNA method. These studies indicated that the TAF-I alpha promoter is under the control of Sp1. (C) 2008 Elsevier Inc. All rights reserved.