ASCL2
Identifiers
Aliases	ASCL2, ASH2, HASH2, MASH2, bHLHa45, achaete-scute family bHLH transcription factor 2
External IDs	OMIM: 601886 MGI: 96920 HomoloGene: 3789 GeneCards: ASCL2
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.5 Start 2,268,498 bp[1] End 2,270,588 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 F5|7 88.08 cM Start 142,520,566 bp[2] End 142,523,001 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland monocyte palpebral conjunctiva blood amniotic fluid skin of abdomen jejunal mucosa skin of limb duodenum seminal vesicula Top expressed in trophoblasts Paneth cell rib lacrimal gland female urethra basisphenoid human mandible parotid gland duodenum pretectal area More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein dimerization activity RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific E-box binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor binding Cellular component nucleus RNA polymerase II transcription regulator complex cytoplasm Biological process cell differentiation spongiotrophoblast layer development response to hypoxia regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II transcription, DNA-templated nervous system development multicellular organism development regulation of neurogenesis in utero embryonic development placenta development negative regulation of Schwann cell proliferation somatic stem cell population maintenance spongiotrophoblast differentiation sensory organ development neuron differentiation positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 430 17173 Ensembl ENSG00000183734 ENSMUSG00000009248 UniProt Q99929 O35885 RefSeq (mRNA) NM_005170 NM_008554 RefSeq (protein) NP_005161 NP_032580 Location (UCSC) Chr 11: 2.27 – 2.27 Mb Chr 7: 142.52 – 142.52 Mb PubMed search [3] [4]
Wikidata
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Achaete-scute complex homolog 2 (Drosophila), also known as ASCL2, is an imprinted human gene.^[5]

Function

This gene is a member of the basic helix-loop-helix (BHLH) family of transcription factors. It activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. Involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system.^[5]

Ascl2 plays a critical role in early gestation, with its products showing up in the oocyte and the two-cell stage of the zygote. This gene has its primary role after implantation of the developing embryo. It is expressed in trophoblast cells on the maternal allele. Its expression is required for the progenitor cells within the ectoplacental cone (EPC), which establishes the first functional maternal-fetal interactions before placental development is completed. The ectoplacental cone continues to develop and differentiate into other cell types which express the Ascl2 gene in the differentiated derivatives. It is specifically found in the spongiotrophoblast cells of the junctional zone. In the mature placenta, glycogen trophoblast (Gly2) cells are found in the junctional zone. Without Ascl2, the GlyT cells are not found and even though these cells develop later in gestation, its progenitor cells are established early on. If a null allele is inherited, the embryo will fail to develop. Insufficient Ascl2 function is also associated with a placenta that has phenotypic defects, which leads to growth retardation.^[6]

Achaete-scute complex homolog 2 (ASCL2) is a maternally expressed imprinted gene that codes is a part of the basic helix-loop-helix (BHLH) transcription factor family. ASCL2 is particularly important during implantation of the developing embryo, specifically in placental development and neuronal precursor determination. Loss of function of ASCL2 will result in embryonic failure. In 2006, ASCL2 was observed to be involved in tumor progression, specifically, ASCL2 was reported to be upregulated in colorectal tumors (Jubb et al). In 2010, Tian et al reported that ASCL2’s involvement in metastasis could be attributed by ASCL2-promoted cellular self-renewal as opposed to cellular differentiation. In 2019, Farmarzi reported a potential link between ASCL2 and breast cancer tumorigenesis which had never previously been demonstrated. ASCL2 expression was noted in multiple breast cancer cell lines, most notably in MCF7 cells. siRNA KO of ASCL2 was shown to inhibit cellular migration of breast cancer cells. Further, ASCL2 knockdown altered the expression of BIRC5 and CD44, which are Wnt-associated genes.

Interactions

ASCL2 has been shown to interact with NCOA6^[7] and RBBP5.^[7]