Expression of mouse Lin28 gene is epigenetically regulated by histone modification

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NICHD	EPIGEN/TRANS/CHROM-4

Authors

• A.L. Pang
• A. Title
• O.M. Rennert

Abstract

The RNA-binding protein Lin28 is considered to be a “stemness” marker. The expression of Lin28 gene predominantly occurs in pluripotent cells and cancer cells. Nevertheless, the regulation of Lin28 gene expression has not been thoroughly studied. We examined whether the expression of Lin28 is epigenetically regulated. Bisulfite-sequencing analysis did not reveal a correlation between its promoter DNA methylation and expression of Lin28 gene. Consistent with this observation, Lin28 expression was not reactivated in non-Lin28 expressing cells (e.g. NIH/3T3 cells) after treatment with 5-aza-2’-deoxycytidine. On the contrary, treatment of NIH/3T3 cells with trichostatin A (TSA) led to the reactivation of Lin28 expresssion. The promoter region of Lin28 gene also became more sensitive to nuclease digestion after TSA treatment, suggesting that Lin28 expression was mediated by the relaxation of chromatin. In agreement with these findings, we observed a significant enrichment of H3K9ac and reduced occupancy of H3K9me2 at the Lin28 promoter region in TSA-treated NIH/3T3 cells and in undifferentiated P19 embryonal carcinoma cells. The opposite pattern of histone modification was found in untreated NIH/3T3 cells and differentiated P19 cells. Our results identify that Lin28 expression in mouse cells is epigenetically regulated by histone modification.

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