Nucleosome-binding protein HMGN4 increases oncogenic activity by inhibiting the expression of E2F-target genes

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NCI	MOLBIO-11

Authors

• JE Kugler
• T Furusawa
• M Bustin

Abstract

HMGN gene family includes the largest set of retropseudogenes in the human genome. HMGN4 protein is a product of one of those retrogenes. It shares basic properties with all other four members of the HMGN family. In humans, the expression of the HMGN4 was noted to be associated with several types of tumors, most notably with thyroid tumor. Here, we over-expressed HMGN4 in mouse embryonic fibroblasts seeking for molecular defects which can contribute to increased tumorigenic potential. The mouse fibroblasts over-expressing HMGN4 has altered transcriptional profile, with prominent deregulation of the expression of several tumor suppressor genes, with slightly decreased sensitivity to the digestion by DNase I at the promoters. This cohort of HMGN4-altered tumor suppressor genes possesses a distinct signature of transcription factor binding sites, majoring E2F family. ChIP-qPCR data have shown markedly decreased binding of E2F1 to the promoters of fore-mentioned genes in HMGN4-MEFs. A potential contribution of HMGN4 expression to cancer has been explored. The over-expression of HMGN4 leads to increased soft-agar colony formation in both human thyroid cancer cells and mouse embryonic fibroblasts. The latter cells formed significantly larger tumors than control MEFs when injected into nude mice.

back to top