General Information of the m6A Target Gene (ID: M6ATAR00757)
Target Name Class E basic helix-loop-helix protein 41 (BHLHE41)
Synonyms
BHLHB3; DEC2; SHARP1; Class E basic helix-loop-helix protein 41; bHLHe41 ; Class B basic helix-loop-helix protein 3; bHLHb3 ; Differentially expressed in chondrocytes protein 2; hDEC2 ; Enhancer-of-split and hairy-related protein 1; SHARP-1
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Gene Name BHLHE41
Chromosomal Location 12p12.1
Function
Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).
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Gene ID 79365
Uniprot ID
BHE41_HUMAN
HGNC ID
HGNC:16617
Ensembl Gene ID
ENSG00000123095.6
KEGG ID
hsa:79365
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
BHLHE41 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Cytokine-cytokine receptor interaction hsa04060
Chemokine signaling pathway hsa04062
Cell Process Cell immunity
Cell growth
Cell migration
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
MC-38 Mouse colon adenocarcinoma Mus musculus CVCL_B288
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model METTL3 knockout or control CT26 and MC38 cells were injected subcutaneously into the dorsal flank of each 4- to 6-week-old male immunocompetent BALB/c and C57BL/6 mice, respectively. Anti-Gr-1 (BE0075; Bio-X-Cell, Lebanon, NH) or immunoglobulin (Ig)G isotype control (BE0090, Bio-XCell) was given every other day via intraperitoneal injection (150 ug/mouse). SB-265610 (Tocris, Bristol, UK) or phosphate-buffered saline was administrated through intraperitoneal injections at a dosage of 2 mg/kg per day. Tumor sizes were measured every other day. To establish an orthotopic mouse model of CRC, 5- to 6-week-old male C57BL/6 mice were treated with 1.7% dextran sodium sulfate in drinking water for 5 days, and then allowed to recover for 3 days. After 24 hours of fasting, METTL3 knockout or control MC38 cells suspended in 50 ul of 1 mg/mL Matrigel-phosphate-buffered saline (Corning, Corning, NY) were instilled into the colon lumen of anesthetized mice, coated sparingly with Vaseline.
Colorectal cancer [ICD-11: 2B91]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Cytokine-cytokine receptor interaction hsa04060
Chemokine signaling pathway hsa04062
Cell Process Cell immunity
Cell growth
Cell migration
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
MC-38 Mouse colon adenocarcinoma Mus musculus CVCL_B288
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model METTL3 knockout or control CT26 and MC38 cells were injected subcutaneously into the dorsal flank of each 4- to 6-week-old male immunocompetent BALB/c and C57BL/6 mice, respectively. Anti-Gr-1 (BE0075; Bio-X-Cell, Lebanon, NH) or immunoglobulin (Ig)G isotype control (BE0090, Bio-XCell) was given every other day via intraperitoneal injection (150 ug/mouse). SB-265610 (Tocris, Bristol, UK) or phosphate-buffered saline was administrated through intraperitoneal injections at a dosage of 2 mg/kg per day. Tumor sizes were measured every other day. To establish an orthotopic mouse model of CRC, 5- to 6-week-old male C57BL/6 mice were treated with 1.7% dextran sodium sulfate in drinking water for 5 days, and then allowed to recover for 3 days. After 24 hours of fasting, METTL3 knockout or control MC38 cells suspended in 50 ul of 1 mg/mL Matrigel-phosphate-buffered saline (Corning, Corning, NY) were instilled into the colon lumen of anesthetized mice, coated sparingly with Vaseline.
References
Ref 1 METTL3 Inhibits Antitumor Immunity by Targeting m(6)A-BHLHE41-CXCL1/CXCR2 Axis to Promote Colorectal Cancer. Gastroenterology. 2022 Jun 11:S0016-5085(22)00629-1. doi: 10.1053/j.gastro.2022.06.024. Online ahead of print.