[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-460516-105":59,"doc-detail-460516-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","maz-regulates-fetal-hemoglobin-repression-by-activating-myb-transcription","MAZ regulates fetal hemoglobin repression by activating MYB transcription","","β-hemoglobinopathies such as sickle cell disease and β-thalassemia are major genetic disorders with high morbidity and mortality, and increasing fetal hemoglobin (HbF) is a promising therapeutic strategy. This study identifies Myc-associated zinc finger (MAZ) as an indirect repressor of γ-globin (HBG) expression in human erythroid cells. MAZ depletion in HUDEP-2 and patient-derived β-thalassemia cells increases HBG mRNA and protein, raising HbF percentages and HbF+ erythroid cells. MAZ occupies the MYB promoter, and altering MYB levels modulates HBG silencing, defining the MAZ-MYB axis as a potential target to enhance HbF.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/maz-regulates-fetal-hemoglobin-repression-by-activating-myb-transcription/460516/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/maz-regulates-fetal-hemoglobin-repression-by-activating-myb-transcription/460516.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-11","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does MAZ play in γ-globin (HBG) regulation?","Question",{"text":113,"@type":114},"MAZ acts as an indirect repressor of HBG expression in human erythroid cells. Reduced MAZ increases HBG mRNA and protein, leading to higher HbF levels.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does MAZ influence MYB in this study?",{"text":118,"@type":114},"MAZ occupies the promoter region of MYB and regulates MYB levels. When MAZ is depleted, MYB levels decrease, and restoring MYB re-silences HBG.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is increasing fetal hemoglobin (HbF) considered therapeutic for these disorders?",{"text":122,"@type":114},"Sustained HbF expression can alleviate the clinical manifestations of β-thalassemia and sickle cell disease by compensating for defects in adult hemoglobin production.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},460516,1790884300,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nMAZ regulates fetal hemoglobin repression by activating MYB transcription  \nDian Lu1,2,4, Yinghong Yang1,4, Bo Yang1, Diyu Chen1, Mingming Zhu1, Siqi Huang1, Jun Hu3, Lifen Zhu1, Weimin Fan1, Yingjun Xie1, Bing Song1, Peng Huang1􀀍 & Xiaofang Sun1􀀍  \nβ-hemoglobinopathies, such as sickle cell disease and β-thalassemia, are common genetic disorders remaining significant global health challenges due to their associated morbidity and mortality. Increasing fetal hemoglobin (HbF) levels has emerged as a promising therapeutic strategy for these disorders. In this study, we report Myc-associated zinc finger (MAZ) as an indirect repressor of γ-globin (HBG) expression in human erythroid cells. Depletion of MAZ in HUDEP-2 and patient-derived β -thalassemia cells leads to significant inductions of both HBG mRNA and protein levels, resulting in increased HbF percentages and HbF + erythroid cells. We demonstrate that MAZ occupies atthe promoter of MYB, a well-known HBG repressor. MAZ depletion reduced MYB levels. Restoration of MYB re-silenced the HBG levels in MAZ depleted cells. Our findings uncover the MAZ-MYB axis in HBG regulation, highlighting MAZ as a potential target to enhance HbF levels in patients with hemoglobin disorders.  \nKeywords MAZ, Fetal hemoglobin (HbF), MYB, β-thalassemia, Sickle cell disease  \nHemoglobinopathies are a group of inherited blood disorders characterized by abnormalities in hemoglobin structure or production, significantly impacting oxygen transport in the body. Two prominent examples are β -thalassemia and sickle cell disease (SCD). β-thalassemia is a common genetic disorder characterized by reduced (β+) or absent (β0) synthesis of β-globin (HBB) chains, leading to a deficiency in hemoglobin1. The severity of the disease is primarily influenced by the excess of unbound α-globin (HBA) chains, which precipitate in red blood cell precursors, resulting in mechanical and oxidative damage, a condition known as ineffective erythropoiesis. SCD arises from a mutation in the HBB gene, resulting in the production of hemoglobin S, which causes red blood cells to deform into a sickle shape under low oxygen conditions2,3. This deformation leads to painful vaso-occlusive crises and hemolytic anemia. Current treatment strategies for β-thalassemia include regular blood transfusions, iron chelation therapy to manage iron overload, hematopoietic stem cell transplantation, and in some cases, gene therapy which offers the potential for a cure4,5. For SCD, currently available treatments are limited to transfusions and hydroxyurea, although stem cell transplantation might bea potentially curative therapy. Several new therapeutic options are available, including gene therapy and gene editing3,6. Both disorders exemplify the diverse manifestations of hemoglobin abnormalities and highlight the importance of understanding their genetic underpinnings for developing effective treatments.  \nTo adapt to the changing oxygen demands of the developing fetus and the newborn after birth, an essential biological process called hemoglobin switching plays a key role during development7. Hemoglobin switching, the perinatal transition from fetal hemoglobin (HbF, α₂γ₂) to adult hemoglobin (HbA, α₂β₂), is a key developmental event.This process is crucial in the context of β-thalassemia and SCD, as raising HbF levels can alleviate symptoms associated with HBB deficiency8. Studies have shown that sustained expression of HbF can significantly ameliorate the clinical manifestations of β-thalassemia and SCD, providing a therapeutic strategy for treating affected individuals9. Genome-editing approaches aimed to correct the disease-causing mutation or reactivate HbF are progressing from early development to clinical approval10–12.  \n1Department of Obstetrics and Gynecology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research C","cbCaimSMPAtUCiqP","https://ap.wps.com/l/cbCaimSMPAtUCiqP","pdf",6062204,"English","# Background and significance\n## Hemoglobinopathies and HbF as therapy\n## Hemoglobin switching and γ-globin repression\n# Known regulatory factors\n## Roles of MYB, BCL11A and epigenetic regulators\n# Study approach and findings\n## MAZ as an HbF/HBG regulator\n## MAZ binding to the MYB promoter\n## Functional rescue via MYB re-silencing","[{\"question\":\"What role does MAZ play in γ-globin (HBG) regulation?\",\"answer\":\"MAZ acts as an indirect repressor of HBG expression in human erythroid cells. Reduced MAZ increases HBG mRNA and protein, leading to higher HbF levels.\"},{\"question\":\"How does MAZ influence MYB in this study?\",\"answer\":\"MAZ occupies the promoter region of MYB and regulates MYB levels. When MAZ is depleted, MYB levels decrease, and restoring MYB re-silences HBG.\"},{\"question\":\"Why is increasing fetal hemoglobin (HbF) considered therapeutic for these disorders?\",\"answer\":\"Sustained HbF expression can alleviate the clinical manifestations of β-thalassemia and sickle cell disease by compensating for defects in adult hemoglobin production.\"}]","MAZ regulates fetal hemoglobin repression by activating MYB transcription | PDF",1790758654,33]