HEYL Antibodies

Background

The HEYL protein encoded by the HEYL gene is a member of the bHLH transcription factors in the HES-related family and mainly acts as an effector factor of the Notch signaling pathway, playing a regulatory role in the development of various tissues and organs. This protein participates in key biological processes such as cell differentiation, tissue pattern establishment, and stem cell maintenance by binding to the specific DNA sequence box E and inhibiting the transcription of downstream target genes. During embryonic development, the expression of HEYL is particularly important for the normal morphogenesis of the cardiovascular system, nervous system and kidneys, and its functional abnormalities have been confirmed to be associated with a variety of congenital defects and diseases. Since its identification in the early 21st century, researchers have gradually revealed the core position of HEYL in the developmental regulatory network through gene knockout models and molecular biology techniques, providing an important theoretical basis for understanding transcriptional suppression mechanisms and cell fate determination.

Structure Function Application Advantage Our Products

Structure of HEYL

The HEYL protein is a transcription factor with a molecular weight of approximately 30-35 kDa. This protein belongs to the bHLH-Orange superfamily. Its molecular weight is relatively conserved among different mammals, and the main difference lies in the amino acid substitution in the non-domain region.

Species	Human	Mouse	Rat	Bovine
Molecular Weight (kDa)	33.2	33.1	33.3	33.0
Primary Structural Differences	Two key domain structure containing bHLH and Orange	The bHLH domain is highly conserved	There is a single amino acid variation in the Orange domain	The similarity to the human sequence reaches 95%

The HEYL protein is composed of approximately 300 amino acids. The core of its three-dimensional structure is the bHLH domain (basic helical-ring-helical), which forms a typical helical-rotation-helical conformation and is responsible for DNA binding and dimerization. The adjacent Orange domain presents a special cyclic conformation that can stabilize protein-protein interactions. These two domains together form the functional core of HEYL: the bHLH region recognizes and binds to the E-box sequence (CANNTG), while the Orange domain mediates interactions with other transcriptional co-repressors, thereby achieving precise regulation of gene expression.

Fig. 1:HEYL mediates NOTCH3-driven meniscus fibrosis. Fig. 1 HEYL mediates NOTCH3-driven meniscus fibrosis.¹

Key structural properties of HEYL:

The conserved bHLH (basic helix-loop-helix) domain is responsible for DNA recognition and binding
Orange structure domain specificity protein interaction interface
Basic amino acid area mediates the specificity of the target genes E box sequence identification
Spiral - ring - helical conformation to inhibit transcription complex assembly structure

Functions of HEYL

The core function of the HEYL gene is to act as a transcriptional suppressor of the Notch signaling pathway and participate in cell fate determination. Meanwhile, this gene plays a regulatory role in a variety of physiological and pathological processes.

Function	Description
Transcriptional inhibition	By binding to the E-box sequence, the transcriptional activity of downstream target genes is inhibited.
Regulation of cell differentiation	Prevent premature cell differentiation in various tissues and organs and maintain the pool of progenitor cells.
Formation of developmental patterns	Participate in the process of boundary establishment and morphogenesis in organ development.
Disease association	The abnormal expression is closely related to a variety of cancer development.
Signal path integration	Coordinate the interaction between Notch signaling and other developmental pathways.

HEYL and its family members HES/HEY have both overlapping and specific functions: compared with HES protein which mainly binds to n-box sequences, HEYL specifically recognizes E-box and has a stronger transcriptional inhibitory ability. This functional differentiation enables HEYL to play an irreplaceable regulatory role in specific developmental stages and tissues.

Applications of HEYL and HEYL Antibody in Literature

1. Han, Liangfeng, et al. "HEYL regulates neoangiogenesis through overexpression in both breast tumor epithelium and endothelium." Frontiers in Oncology 10 (2021): 581459. https://doi.org/10.3389/fonc.2020.581459

Research has found that the HEYL gene promotes angiogenesis and progression of breast cancer by directly up-regulating factors such as CXCL1/2/3. Inhibiting HEYL or its downstream signals can effectively suppress tumor blood vessels and growth, suggesting it as a new target for anti-vascular therapy.

2. Fadel, Hewida H., et al. "Partial‐Methylated HeyL Promoter Predicts the Severe Illness in Egyptian COVID‐19 Patients." Disease Markers 2022.1 (2022): 6780710. https://doi.org/10.1155/2022/6780710

Studies have found that the HeyL gene promoter in Egyptian COVID-19 patients is in a unique "hypomethylation" state, which may enhance its gene activity and be associated with severe symptoms such as fever and pneumonia. The methylation status of HeyL may serve as a prognostic marker.

3. Lin, Qimei, et al. "The HeyL-aromatase axis promotes cancer stem cell properties by endogenous estrogen-induced autophagy in castration-resistant prostate cancer." Frontiers in Oncology 11 (2022): 787953. https://doi.org/10.3389/fonc.2021.787953

Research has found that HEYL directly activates the CYP19A1 gene in castration-resistant prostate cancer, increasing the levels of aromatase and endogenous estrogen, thereby promoting the characteristics and drug resistance of cancer stem cells. Targeting this pathway may become a new therapeutic strategy.

4. Bodas, Manish, et al. "The NOTCH3 downstream target HEYL is required for efficient human airway basal cell differentiation." Cells 10.11 (2021): 3215. https://doi.org/10.3390/cells10113215

Research has found that HEYL, a downstream target of NOTCH3 signaling, is a key factor in regulating the differentiation of airway basal cells. Knockdown of HEYL can damage the differentiation of various epithelial cells such as goblet cells and ciliated cells, while overexpression of HEYL in COPD cells can reverse their differentiation disorders.

5. Brahim, Sonia, et al. "Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer." Cell Death & Disease 14.2 (2023): 171. https://doi.org/10.1038/s41419-023-05674-7

Research has found that Notch3 inhibits the cell cycle regulator Mybl2 through its downstream target HEYL, thereby delaying the occurrence of breast cancer. Notch3 deletion accelerates tumor formation, revealing the protective role of the Notch3-Heyl pathway in breast cancer.

Creative Biolabs: HEYL Antibodies for Research

Creative Biolabs specializes in the production of high-quality HEYL antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom HEYL Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our HEYL antibodies, custom preparations, or technical support, contact us at email.

Reference

Sun, Hao, et al. "Silencing of NOTCH3 signaling in meniscus smooth muscle cells inhibits fibrosis and exacerbates degeneration in a HEYL‐dependent manner." Advanced Science 10.16 (2023): 2207020. https://doi.org/10.1002/advs.202207020