title: Sox2 function as a negative regulator to control HAMP expression.
abstract: BACKGROUND
  Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore, it is an important goal to understand the mechanisms controlling HAMP gene expression.
  
  
  RESULTS
  Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes.
  
  
  CONCLUSIONS
  We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. smmusb@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. angelbq@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bian
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. schhao@133sh.com.
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Shao
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. laa2001@163.com.
authors.forename: An-An
authors.initials: AA
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. jingwei7777@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. huangliur@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. yijie06@medmail.com.cn.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. Yingqizhou@163.com.
authors.forename: Ying-Qi
authors.initials: YQ
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. li_gang169@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. gangjinsh@yeah.net.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
mesh_terms: D000740:Anemia / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D064451:Hepcidins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008156:Luciferases; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D007501:Iron; D008156:Luciferases