ASCL1
Description
The ASCL1 (achaete-scute family bHLH transcription factor 1) is a protein-coding gene located on chromosome 12.
ASCL1, also known as Achaete-scute homolog 1, is a protein encoded by the ASCL1 gene in humans. It is a member of the basic helix-loop-helix (BHLH) family of transcription factors, known for activating transcription by binding to the E box (5'-CANNTG-3'). ASCL1 requires dimerization with other BHLH proteins for efficient DNA binding. It plays a crucial role in neuronal commitment and differentiation, particularly in the generation of olfactory and autonomic neurons. ASCL1 is highly expressed in medullary thyroid cancer and small cell lung cancer, making it a potential marker for these cancers. The presence of a CAG repeat in the gene suggests a possible involvement in tumor formation. The development of the vertebrate nervous system starts with the formation of the neural tube in the early embryo. This neural tube eventually gives rise to the entire nervous system, but first, neuroblasts must differentiate from the neuroepithelium of the tube.
ASCL1 is a transcription factor that plays a pivotal role in neuronal differentiation. It functions as a pioneer transcription factor, opening up tightly packed chromatin to enable other factors to bind and activate neural pathways. ASCL1 directly binds to the E box motif (5'-CANNTG-3') on gene promoters, stimulating the transcription of neuronal genes. Notably, a combination of three transcription factors, ASCL1, POU3F2/BRN2, and MYT1L, has been shown to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in laboratory settings. ASCL1 contributes to the development of specific neural lineages in various regions of the central nervous system (CNS) and in multiple lineages within the peripheral nervous system (PNS) at early developmental stages. It is essential for the generation of olfactory and autonomic neurons. ASCL1 acts synergistically with FOXN4 to determine the identity of V2b neurons, rather than V2a, from bipotential p2 progenitors during spinal cord neurogenesis. This is likely mediated by the activation of DLL4-NOTCH signaling. ASCL1 is also involved in the regulation of neuroendocrine cell development within the glandular stomach.
ASCL1 is also known as ASH1, HASH1, MASH1, bHLHa46.
