Furthermore, it was also observed that there was a chromatin repressive complex composed by JARID1B
demethylase and by HDAC1 deacetylase.
These strategies include the targeting of the histone demethylase jumonji, AT rich interactive domain 1B (JARID1B), which we found to be functionally significant in the maintenance of cancer stem cells.
Drug development targeting the histone demethylase JARID1B
We and others have previously found the highly conserved histone demethylase, jumonji AT rich interactive domain 1B (JARID1B) to be a functional marker of cancer stem cells.
JARID1B belongs to a family of Jarid1 proteins that are highly homologous, and there is at least partial redundancy between Jarid1b and Jarid1a in demethylating H3K4.
H3K4 is demethylated by the KDM1 family (LSD1 and AOF1), the KDM2 family (FBXL10), and the KDM5 family (JARID1A, JARID1B
, JARID1C, and JARID1D) as well as JARID2 and NO66.
Wang et al., "H3K4 demethylation by Jarid1a and Jarid1b
contributes to retinoblastoma-mediated gene silencing during cellular senescence," Proceedings of the National Academy of Sciences of the United States of America, vol.
Other examples of tumor cell plasticity include the demonstration that melanoma cells expressing the histone demethylase JARID1B
are required for continuous tumor growth, and that such JARID1B-positive cells can spontaneously arise from JARID1B-negative cells (57).
Current study by Bustos and colleagues have demonstrated that JARID1B
(Jumonji AT-rich interactive domain 1B) histone demethylase represses Runx2 in undifferentiated WJ-MSCs.
Lysine specific demethylase 1 (LSD1) and Jumonji domain containing proteins (JMJD1A, JMJD2, JMJD3/UTX, and JARID1B) are two major histone demethylases (HDMTs) that have been identified to erase methylation from histone proteins in HCC .
LSD1 and JmjC domain containing H3K4 histone demethylase Jumonji AT-rich interactive domain 1B (JARID1B) are erasers for mono-, di-, and trimethylation of H3K4 (Figure 1).
Yan, "Histone demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes," Journal of Biological Chemistry, vol.