A novel downstream positive regulatory element mediating transcription of the human high mobility group (HMG) I‐C gene

The high mobility group (HMG) I proteins are small, non‐histone chromosomal proteins that promote gene activation during development and within rapidly dividing cells. They do so by facilitating enhanceosome formation on inducible genes, via both protein/DNA and protein/protein interactions. The HMG I‐C gene is tightly regulated, normally being expressed exclusively during embryonic development. However, HMG I‐C expression is also observed frequently in a number of tumor types, and this expression has been shown to contribute to the malignant transformation process. With the aim of dissecting pathways that lead to aberrant expression of HMG I‐C in tumor cells, we have analyzed HMG I‐C gene regulation in the human hepatoma cell line PLC/PRF/5. One of the two HMG I‐C transcripts detected in this cell line originates from a novel downstream initiation site at nucleotide −161 relative to the first methionine. Transcription from the downstream initiation site is mediated by a PRE located between nt −222 and −217. We show here that the Sp1 and Sp3 transcription factors interact with the PRE and transactivate the HMG I‐C promoter in a cooperative fashion. This study provides the first characterization of this downstream HMG I‐C promoter.