ASCL2
Description
The ASCL2 (achaete-scute family bHLH transcription factor 2) is a protein-coding gene located on chromosome 11.
ASCL2, also known as Achaete-scute complex homolog 2 (Drosophila), is an imprinted human gene. It is a member of the basic helix-loop-helix (BHLH) family of transcription factors. ASCL2 activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. ASCL2 is involved in the determination of neuronal precursors in the peripheral nervous system and the central nervous system. 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.
ASCL2 is a transcription factor that binds to E-box motifs (5'-CANNTG-3') in the regulatory elements of target genes. It likely does this as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3. ASCL2 can bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes. ASCL2 is required during post-implantation development for the generation of some differentiated trophoblast cell types. The transcriptional activity of ASCL2 may be antagonized in a subset of trophoblast cells by the bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins. ASCL2 is involved in the differentiation and function of follicular T-helper (Tfh) cells, playing a role in germinal center responses. It probably modulates the expression of genes involved in Tfh cell function, such as BCL6. ASCL2 may also act as a suppressor of Th1-, Th2-, and Th17-cell differentiation. It induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin. ASCL2 may form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R-spondin signaling, and thereby maintaining stem cell characteristics. It modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up-regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells. ASCL2 may play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C. ASCL2 may be dispensable for blastocyst formation and later embryonic function. ASCL2 may be involved in the determination of neuronal precursors. {ECO:0000250|UniProtKB:O35885, ECO:0000250|UniProtKB:P19360}
ASCL2 is also known as ASH2, HASH2, MASH2, bHLHa45.
