Publication

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3

Pasricha, S-R., Lim, P. J., Duarte, T. L., Casu, C., Oosterhuis, D., Mleczko-Sanecka, K., Suciu, M., Da Silva, A. R., Al-Hourani, K., Arezes, J., McHugh, K., Gooding, S., Frost, J. N., Wray, K., Santos, A., Porto, G., Repapi, E., Gray, N., Draper, S. J., Ashley, N., Soilleux, E., Olinga, P., Muckenthaler, M. U., Hughes, J. R., Rivella, S., Milne, T. A., Armitage, A. E. & Drakesmith, H. 1-Sep-2017 In : Nature Communications. 8, 15 p., 403

Research output: Scientific - peer-reviewArticle

APA

Pasricha, S-R., Lim, P. J., Duarte, T. L., Casu, C., Oosterhuis, D., Mleczko-Sanecka, K., ... Drakesmith, H. (2017). Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nature Communications, 8, [403]. DOI: 10.1038/s41467-017-00500-z

Author

Pasricha, Sant-Rayn; Lim, Pei Jin; Duarte, Tiago L; Casu, Carla; Oosterhuis, Dorenda; Mleczko-Sanecka, Katarzyna; Suciu, Maria; Da Silva, Ana Rita; Al-Hourani, Kinda; Arezes, João; McHugh, Kirsty; Gooding, Sarah; Frost, Joe N; Wray, Katherine; Santos, Ana; Porto, Graça; Repapi, Emmanouela; Gray, Nicki; Draper, Simon J; Ashley, Neil; Soilleux, Elizabeth; Olinga, Peter; Muckenthaler, Martina U; Hughes, Jim R; Rivella, Stefano; Milne, Thomas A; Armitage, Andrew E; Drakesmith, Hal / Hepcidin is regulated by promoter-associated histone acetylation and HDAC3.

In: Nature Communications, Vol. 8, 403, 01.09.2017.

Research output: Scientific - peer-reviewArticle

Harvard

Pasricha, S-R, Lim, PJ, Duarte, TL, Casu, C, Oosterhuis, D, Mleczko-Sanecka, K, Suciu, M, Da Silva, AR, Al-Hourani, K, Arezes, J, McHugh, K, Gooding, S, Frost, JN, Wray, K, Santos, A, Porto, G, Repapi, E, Gray, N, Draper, SJ, Ashley, N, Soilleux, E, Olinga, P, Muckenthaler, MU, Hughes, JR, Rivella, S, Milne, TA, Armitage, AE & Drakesmith, H 2017, 'Hepcidin is regulated by promoter-associated histone acetylation and HDAC3' Nature Communications, vol 8, 403. DOI: 10.1038/s41467-017-00500-z

Standard

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. / Pasricha, Sant-Rayn; Lim, Pei Jin; Duarte, Tiago L; Casu, Carla; Oosterhuis, Dorenda; Mleczko-Sanecka, Katarzyna; Suciu, Maria; Da Silva, Ana Rita; Al-Hourani, Kinda; Arezes, João; McHugh, Kirsty; Gooding, Sarah; Frost, Joe N; Wray, Katherine; Santos, Ana; Porto, Graça; Repapi, Emmanouela; Gray, Nicki; Draper, Simon J; Ashley, Neil; Soilleux, Elizabeth; Olinga, Peter; Muckenthaler, Martina U; Hughes, Jim R; Rivella, Stefano; Milne, Thomas A; Armitage, Andrew E; Drakesmith, Hal.

In: Nature Communications, Vol. 8, 403, 01.09.2017.

Research output: Scientific - peer-reviewArticle

Vancouver

Pasricha S-R, Lim PJ, Duarte TL, Casu C, Oosterhuis D, Mleczko-Sanecka K et al. Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nature Communications. 2017 Sep 1;8. 403. Available from, DOI: 10.1038/s41467-017-00500-z


BibTeX

@article{297e46c28853483cb61e77e989024bc6,
title = "Hepcidin is regulated by promoter-associated histone acetylation and HDAC3",
abstract = "Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both involve reversible loss of H3K9ac and H3K4me3 at the hepcidin locus. In vitro, pan-histone deacetylase inhibition elevates hepcidin expression, and in vivo maintains H3K9ac at hepcidin-associated chromatin and abrogates hepcidin suppression by erythropoietin, iron deficiency, thalassemia, and hemochromatosis. Histone deacetylase 3 and its cofactor NCOR1 regulate hepcidin; histone deacetylase 3 binds chromatin at the hepcidin locus, and histone deacetylase 3 knockdown counteracts hepcidin suppression induced either by erythroferrone or by inhibiting bone morphogenetic protein signaling. In iron deficient mice, the histone deacetylase 3 inhibitor RGFP966 increases hepcidin, and RNA sequencing confirms hepcidin is one of the genes most differentially regulated by this drug in vivo. We conclude that suppression of hepcidin expression involves epigenetic regulation by histone deacetylase 3.Hepcidin controls systemic iron levels by inhibiting intestinal iron absorption and iron recycling. Here, Pasricha et al. demonstrate that the hepcidin-chromatin locus displays HDAC3-mediated reversible epigenetic modifications during both erythropoiesis and iron deficiency.",
keywords = "Journal Article",
author = "Sant-Rayn Pasricha and Lim, {Pei Jin} and Duarte, {Tiago L} and Carla Casu and Dorenda Oosterhuis and Katarzyna Mleczko-Sanecka and Maria Suciu and {Da Silva}, {Ana Rita} and Kinda Al-Hourani and João Arezes and Kirsty McHugh and Sarah Gooding and Frost, {Joe N} and Katherine Wray and Ana Santos and Graça Porto and Emmanouela Repapi and Nicki Gray and Draper, {Simon J} and Neil Ashley and Elizabeth Soilleux and Peter Olinga and Muckenthaler, {Martina U} and Hughes, {Jim R} and Stefano Rivella and Milne, {Thomas A} and Armitage, {Andrew E} and Hal Drakesmith",
year = "2017",
month = "9",
doi = "10.1038/s41467-017-00500-z",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Hepcidin is regulated by promoter-associated histone acetylation and HDAC3

AU - Pasricha,Sant-Rayn

AU - Lim,Pei Jin

AU - Duarte,Tiago L

AU - Casu,Carla

AU - Oosterhuis,Dorenda

AU - Mleczko-Sanecka,Katarzyna

AU - Suciu,Maria

AU - Da Silva,Ana Rita

AU - Al-Hourani,Kinda

AU - Arezes,João

AU - McHugh,Kirsty

AU - Gooding,Sarah

AU - Frost,Joe N

AU - Wray,Katherine

AU - Santos,Ana

AU - Porto,Graça

AU - Repapi,Emmanouela

AU - Gray,Nicki

AU - Draper,Simon J

AU - Ashley,Neil

AU - Soilleux,Elizabeth

AU - Olinga,Peter

AU - Muckenthaler,Martina U

AU - Hughes,Jim R

AU - Rivella,Stefano

AU - Milne,Thomas A

AU - Armitage,Andrew E

AU - Drakesmith,Hal

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both involve reversible loss of H3K9ac and H3K4me3 at the hepcidin locus. In vitro, pan-histone deacetylase inhibition elevates hepcidin expression, and in vivo maintains H3K9ac at hepcidin-associated chromatin and abrogates hepcidin suppression by erythropoietin, iron deficiency, thalassemia, and hemochromatosis. Histone deacetylase 3 and its cofactor NCOR1 regulate hepcidin; histone deacetylase 3 binds chromatin at the hepcidin locus, and histone deacetylase 3 knockdown counteracts hepcidin suppression induced either by erythroferrone or by inhibiting bone morphogenetic protein signaling. In iron deficient mice, the histone deacetylase 3 inhibitor RGFP966 increases hepcidin, and RNA sequencing confirms hepcidin is one of the genes most differentially regulated by this drug in vivo. We conclude that suppression of hepcidin expression involves epigenetic regulation by histone deacetylase 3.Hepcidin controls systemic iron levels by inhibiting intestinal iron absorption and iron recycling. Here, Pasricha et al. demonstrate that the hepcidin-chromatin locus displays HDAC3-mediated reversible epigenetic modifications during both erythropoiesis and iron deficiency.

AB - Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both involve reversible loss of H3K9ac and H3K4me3 at the hepcidin locus. In vitro, pan-histone deacetylase inhibition elevates hepcidin expression, and in vivo maintains H3K9ac at hepcidin-associated chromatin and abrogates hepcidin suppression by erythropoietin, iron deficiency, thalassemia, and hemochromatosis. Histone deacetylase 3 and its cofactor NCOR1 regulate hepcidin; histone deacetylase 3 binds chromatin at the hepcidin locus, and histone deacetylase 3 knockdown counteracts hepcidin suppression induced either by erythroferrone or by inhibiting bone morphogenetic protein signaling. In iron deficient mice, the histone deacetylase 3 inhibitor RGFP966 increases hepcidin, and RNA sequencing confirms hepcidin is one of the genes most differentially regulated by this drug in vivo. We conclude that suppression of hepcidin expression involves epigenetic regulation by histone deacetylase 3.Hepcidin controls systemic iron levels by inhibiting intestinal iron absorption and iron recycling. Here, Pasricha et al. demonstrate that the hepcidin-chromatin locus displays HDAC3-mediated reversible epigenetic modifications during both erythropoiesis and iron deficiency.

KW - Journal Article

U2 - 10.1038/s41467-017-00500-z

DO - 10.1038/s41467-017-00500-z

M3 - Article

VL - 8

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 403

ER -

ID: 47392791