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HES-1 is an upstream negative regulator of REST expression. HES-1 is an upstream negative regulator of REST expression. HES-1 preserves the long-term reconstituting hematopoietic activity of 34-KSL stem cells ex vivo. Hes1 transcription repression activity is inhibited by Hes6. IkappaBalpha is recruited to the promoter regions of the Notch-target gene, hes1. Notch1 inhibits the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through HES1. These results indicate that the molecular association between HES1-, HEY2- and SIRT1-related proteins is conserved among metazoans, from Drosophila to human, and suggest that the Sir2-bHLH interaction also plays important roles in human cells. This protein belongs to the basic helix-loop-helix family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. The protein has a particular type of basic domain that contains a helix interrupting protein that binds to the N-box rather than the canonical E-box. The estrogen receptor and AhR signaling pathways regulate HES-1, but with opposing effects, suggests the existence of a new pathway by which AhR represses E2-signaling.
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