Sox2 function as a negative regulator to control HAMP expression

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,itis a...

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Autores principales:	Song,Bin, Bian,Qi, Shao,Cheng-Hao, Liu,An-An, Jing,Wei, Liu,Rui, Zhang,Yi-Jie, Zhou,Ying-Qi, Li,Gang, Jin,Gang
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2015
Materias:	Sox2 Gene expression Hepatocyte HAMP Iron metabolism
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100023
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spelling	oai:scielo:S0716-976020150001000232016-02-16Sox2 function as a negative regulator to control HAMP expressionSong,BinBian,QiShao,Cheng-HaoLiu,An-AnJing,WeiLiu,RuiZhang,Yi-JieZhou,Ying-QiLi,GangJin,Gang Sox2 Gene expression Hepatocyte HAMP Iron metabolism 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,itis animportant 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. CONCLUSION: 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100023en10.1186/s40659-015-0013-z
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Sox2 Gene expression Hepatocyte HAMP Iron metabolism
spellingShingle	Sox2 Gene expression Hepatocyte HAMP Iron metabolism Song,Bin Bian,Qi Shao,Cheng-Hao Liu,An-An Jing,Wei Liu,Rui Zhang,Yi-Jie Zhou,Ying-Qi Li,Gang Jin,Gang Sox2 function as a negative regulator to control HAMP expression
description	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,itis animportant 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. CONCLUSION: 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.
author	Song,Bin Bian,Qi Shao,Cheng-Hao Liu,An-An Jing,Wei Liu,Rui Zhang,Yi-Jie Zhou,Ying-Qi Li,Gang Jin,Gang
author_facet	Song,Bin Bian,Qi Shao,Cheng-Hao Liu,An-An Jing,Wei Liu,Rui Zhang,Yi-Jie Zhou,Ying-Qi Li,Gang Jin,Gang
author_sort	Song,Bin
title	Sox2 function as a negative regulator to control HAMP expression
title_short	Sox2 function as a negative regulator to control HAMP expression
title_full	Sox2 function as a negative regulator to control HAMP expression
title_fullStr	Sox2 function as a negative regulator to control HAMP expression
title_full_unstemmed	Sox2 function as a negative regulator to control HAMP expression
title_sort	sox2 function as a negative regulator to control hamp expression
publisher	Sociedad de Biología de Chile
publishDate	2015
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100023
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Sox2 function as a negative regulator to control HAMP expression

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