What is it about?
Our data show that histone methyltransferase SETDB1 is critical for preventing transcription factor (TF) activity on cryptic enhancer, in part overlapping with mouse endogenous retrovirus sequences. When SETDB1 is lacking, these cryptic enhancers can become overly active, leading to abnormal expression of nearby genes. This disruption coincides with compromised function of stem cells, altered differentiation of blood cell types, and increased hematopoietic stem cell proliferation. Notably, we demonstrate that SETDB1 acts as a guardian, restricting the unwarranted activity of TFs on these cryptic enhancers and maintaining the proper balance and differentiation of mouse fetal liver hematopoietic stem and progenitor cells.
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Why is it important?
Our results clarify how important the regulation of cryptic enhancers is for controlling blood cell formation and cast a new light on the role of retroviral elements as potential disruptive factors in gene regulation.
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This page is a summary of: Histone methyltransferase SETDB1 safeguards mouse fetal hematopoiesis by suppressing activation of cryptic enhancers, Proceedings of the National Academy of Sciences, December 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2409656121.
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