Two purified factors bind to the same sequence in the enhancer of mouse MHC class I genes: one of them is a positive regulator induced upon differentiation of teratocarcinoma cells

Abstract

The MHC class I murine and beta-2-microglobulin genes are silent in embryonal carcinoma (EC) cells but are induced upon differentiation of these cells. We have previously shown that enhancer-like sequences located in the promoter of the H-2Kb gene are non-functional in F9 and PCC3 cells. We have previously purified a 48 kd protein (KBFI) from a mouse T cell line which binds to a palindromic sequence located in this enhancer and to a similar sequence in the promoter of the beta-2-microglobulin gene. We describe here the purification of a second protein (KBF2, 58 kd) which also binds to this sequence. While both activities are present in differentiated cells, KBF1 binding activity is absent in undifferentiated EC cells, where the palindromic sequence shows no enhancer activity. Upon differentiation, KBF1 binding activity is induced and the palindromic sequence becomes active as an enhancer. Thus, the absence of KBF1 activity in undifferentiated EC cells is at least in part responsible for the lack of expression of H-2 class I and beta-2-microglobulin genes in these cells and suggests that KBF1

Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless.

“…2A, lanes 5-10; data not shown). These results are consistent with data described previously for purified RBP-JK and KBF2 proteins (Israel et al 1989;Tun et al 1994).…”

“…The human protein KBF2 specifically binds as a mono mer to various KB sites and is present in the nuclei of all cells analyzed so far (Israel et al 1989). We have purified this factor and isolated the corresponding cDNA.…”

Differential Expression of Tapasin and Immunoproteasome Subunits in Adenovirus Type 5- Versus Type 12-transformed Cells

“…We have shown previously that transcriptional down-regulation of MHC class I genes can be attributed to the H2TF1 element in the mhcI promoter (25,49,67), which is regulated by NF-B family members (68,69). Consistently, basal NF-B activity is very low in Ad12-transformed cells, and ectopic expression of NF-B1 partially restores MHC class I protein expression (25,40,49).…”

Identification of Genes Involved in the Suppression of Antibody Production from Human Peripheral Blood Lymphocytes

“…7) Although KBF2 is known to bind to the H2K molecule, its function is not completely understood. 8) As shown in Fig. 2, no significant changes in the expression levels of these genes in LLME(À)-or LLME(þ)-PBMCs during the culture period were detected.…”