Fig. 8: Schematic diagram illustrating the regulatory mechanism of liver-TEs in liver cancer cell proliferation. | Nature Communications

Fig. 8: Schematic diagram illustrating the regulatory mechanism of liver-TEs in liver cancer cell proliferation.

From: Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma

Fig. 8

In HCC cells, liver-TEs exhibit high plasticity and regulatory potential, and they are located adjacent to several tumor-suppressive genes. liver-TEs are enriched with motifs recognized by ZMYM3, which recruits the histone demethylase KDM1A. This study focuses on liver-TE-associated genes and the regulatory mechanisms involved in the expression of HNF4A, an important tumor-suppressive gene in HCC. The following mechanisms were illustrated: (1) KDM1A/ZMYM3 recruitment to the transcriptional regulatory region of the HNF4A gene through liver-TE, leading to specific removal of the active histone mark H3K4me1 by KDM1A; (2) KDM1A interacts with HNF4A, thereby suppressing the expression of downstream genes; and (3) liver-TE/ZMYM3/KDM1A promotes HCC cell growth by inhibiting the expression and activity of HNF4A.

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