AI Article Synopsis
- Both type 1 and type 2 diabetes involve the loss of functional beta cells, highlighting the urgent need for strategies to restore them.
- Researchers found that the nuclear receptor TLX can promote beta cell proliferation, but the mechanisms behind it were unclear until they identified specific target genes of TLX using ChIP-Seq.
- One key finding was that E2F6, which is negatively regulated by TLX, inhibits beta cell proliferation, indicating that TLX may enhance beta cell growth by suppressing E2F6's expression.
Article Abstract
Both type 1 and type 2 diabetes are associated with loss of functional beta cell mass, and strategies to restore beta cells are urgently needed. We reported previously that overexpression of the nuclear receptor TLX induces beta cell proliferation, but the underlying molecular mechanism has not been defined. Here, we identified direct targets of TLX in beta cells at the genome-wide level by ChIP-Seq. These targets include a cadre of regulators that are known to be critical for proliferation. Among these ChIP targets, E2F6 was tightly associated with the cell cycle modules, and thus, we further analyzed E2F6 expression and function in beta cells. We showed that E2F6 is strongly downregulated by TLX, and its expression inhibits beta cell proliferation. Moreover, coexpression of E2F6 with TLX partially abrogated the proliferative effects of TLX. These results strongly suggest that TLX acts through E2F6 to regulate beta cell proliferation. Together, the results of this study reveal a direct interaction between TLX and E2F6 and suggest new targets for the expansion of functional beta cell mass.
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| http://dx.doi.org/10.1016/j.bbrc.2019.04.033 | DOI Listing |
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