A Transcriptional Regulatory Role of the THAP11–HCF-1 Complex in Colon Cancer Cell Function

Abstract

The recently identified Thanatos-associated protein (THAP) domain is an atypical zinc finger motif with sequence-specific DNA-binding activity. Emerging data suggest that THAP proteins may function in chromatin-dependent processes, including transcriptional regulation, but the roles of most THAP proteins in normal and aberrant cellular processes remain largely unknown. In this work, we identify THAP11 as a transcriptional regulator differentially expressed in human colon cancer. Immunohistochemical analysis of human colon cancers revealed increased THAP11 expression in both primary tumors and metastases. Knockdown of THAP11 in SW620 colon cancer cells resulted in a significant decrease in cell proliferation, and profiling of gene expression in these cells identified a novel gene set composed of 80 differentially expressed genes, 70% of which were derepressed by THAP11 knockdown. THAP11 was found to associate physically with the transcriptional coregulator HCF-1 (host cell factor 1) and recruit HCF-1 to target promoters. Importantly, THAP11-mediated gene regulation and its chromatin association require HCF-1, while HCF-1 recruitment at these genes requires THAP11. Collectively, these data provide the first characterization of THAP11-dependent gene expression in human colon cancer cells and suggest that the THAP11–HCF-1 complex may be an important transcriptional and cell growth regulator in human colon cancer.

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SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.06033-11.

ACKNOWLEDGMENTS

This work was supported by NIH/NCI grant R01 CA133755 (D.C.). J.B.P. is supported by NIH/NCI Institutional NRSA Training Program in Signal Transduction and Cancer grant T32 CA070085. We gratefully acknowledge the Northwestern University Cell Imaging Facility, Flow Cytometry Facility, and Genomics Core Facility, which are supported by Cancer Center Support grant NCI CA060553.

We have no conflict of interest to declare.