A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure

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Standard

A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure. / Tummala, Hemanth; Walne, Amanda J.; Bewicke-Copley, Findlay; Ellison, Alicia; Pontikos, Nikolas; Bridger, Maria G.; Rio-Machin, Ana; Sidhu, Jasmin K.; Wang, Jun; Hasle, Henrik; Fitzgibbon, Jude; Vulliamy, Tom; Dokal, Inderjeet.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 117, Nr. 29, 07.2020, s. 17151-17155.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Tummala, H, Walne, AJ, Bewicke-Copley, F, Ellison, A, Pontikos, N, Bridger, MG, Rio-Machin, A, Sidhu, JK, Wang, J, Hasle, H, Fitzgibbon, J, Vulliamy, T & Dokal, I 2020, 'A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure', Proceedings of the National Academy of Sciences of the United States of America, bind 117, nr. 29, s. 17151-17155. https://doi.org/10.1073/pnas.2002857117

APA

Tummala, H., Walne, A. J., Bewicke-Copley, F., Ellison, A., Pontikos, N., Bridger, M. G., Rio-Machin, A., Sidhu, J. K., Wang, J., Hasle, H., Fitzgibbon, J., Vulliamy, T., & Dokal, I. (2020). A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure. Proceedings of the National Academy of Sciences of the United States of America, 117(29), 17151-17155. https://doi.org/10.1073/pnas.2002857117

CBE

Tummala H, Walne AJ, Bewicke-Copley F, Ellison A, Pontikos N, Bridger MG, Rio-Machin A, Sidhu JK, Wang J, Hasle H, Fitzgibbon J, Vulliamy T, Dokal I. 2020. A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure. Proceedings of the National Academy of Sciences of the United States of America. 117(29):17151-17155. https://doi.org/10.1073/pnas.2002857117

MLA

Tummala, Hemanth o.a.. "A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure". Proceedings of the National Academy of Sciences of the United States of America. 2020, 117(29). 17151-17155. https://doi.org/10.1073/pnas.2002857117

Vancouver

Tummala H, Walne AJ, Bewicke-Copley F, Ellison A, Pontikos N, Bridger MG o.a. A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure. Proceedings of the National Academy of Sciences of the United States of America. 2020 jul;117(29):17151-17155. https://doi.org/10.1073/pnas.2002857117

Author

Tummala, Hemanth ; Walne, Amanda J. ; Bewicke-Copley, Findlay ; Ellison, Alicia ; Pontikos, Nikolas ; Bridger, Maria G. ; Rio-Machin, Ana ; Sidhu, Jasmin K. ; Wang, Jun ; Hasle, Henrik ; Fitzgibbon, Jude ; Vulliamy, Tom ; Dokal, Inderjeet. / A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure. I: Proceedings of the National Academy of Sciences of the United States of America. 2020 ; Bind 117, Nr. 29. s. 17151-17155.

Bibtex

@article{941cd99d3b83428e905e3ae083af65ea,
title = "A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure",
abstract = "Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (SP1). This heterozygous variant (c.1995delA) truncates the canonical Sp1 molecule in the highly conserved C-terminal DNA-binding zinc finger domains. Transcriptomic analysis and gene promoter characterization in patients' blood revealed a hypermorphic effect of this Sp1 variant, triggering superactivation of Sp1-mediated transcription and driving significant up-regulation of Sp1 target genes. This familial genetic study indicates a central role for Sp1 in causing autosomal dominant transmission of BMF, thereby confirming its critical role in hematopoiesis in humans.",
keywords = "bone marrow failure, Sp1, transcription",
author = "Hemanth Tummala and Walne, {Amanda J.} and Findlay Bewicke-Copley and Alicia Ellison and Nikolas Pontikos and Bridger, {Maria G.} and Ana Rio-Machin and Sidhu, {Jasmin K.} and Jun Wang and Henrik Hasle and Jude Fitzgibbon and Tom Vulliamy and Inderjeet Dokal",
year = "2020",
month = jul,
doi = "10.1073/pnas.2002857117",
language = "English",
volume = "117",
pages = "17151--17155",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "29",

}

RIS

TY - JOUR

T1 - A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure

AU - Tummala, Hemanth

AU - Walne, Amanda J.

AU - Bewicke-Copley, Findlay

AU - Ellison, Alicia

AU - Pontikos, Nikolas

AU - Bridger, Maria G.

AU - Rio-Machin, Ana

AU - Sidhu, Jasmin K.

AU - Wang, Jun

AU - Hasle, Henrik

AU - Fitzgibbon, Jude

AU - Vulliamy, Tom

AU - Dokal, Inderjeet

PY - 2020/7

Y1 - 2020/7

N2 - Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (SP1). This heterozygous variant (c.1995delA) truncates the canonical Sp1 molecule in the highly conserved C-terminal DNA-binding zinc finger domains. Transcriptomic analysis and gene promoter characterization in patients' blood revealed a hypermorphic effect of this Sp1 variant, triggering superactivation of Sp1-mediated transcription and driving significant up-regulation of Sp1 target genes. This familial genetic study indicates a central role for Sp1 in causing autosomal dominant transmission of BMF, thereby confirming its critical role in hematopoiesis in humans.

AB - Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia. By whole-exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcription factor specificity protein 1 (SP1). This heterozygous variant (c.1995delA) truncates the canonical Sp1 molecule in the highly conserved C-terminal DNA-binding zinc finger domains. Transcriptomic analysis and gene promoter characterization in patients' blood revealed a hypermorphic effect of this Sp1 variant, triggering superactivation of Sp1-mediated transcription and driving significant up-regulation of Sp1 target genes. This familial genetic study indicates a central role for Sp1 in causing autosomal dominant transmission of BMF, thereby confirming its critical role in hematopoiesis in humans.

KW - bone marrow failure

KW - Sp1

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=85088880483&partnerID=8YFLogxK

U2 - 10.1073/pnas.2002857117

DO - 10.1073/pnas.2002857117

M3 - Journal article

C2 - 32636268

AN - SCOPUS:85088880483

VL - 117

SP - 17151

EP - 17155

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 29

ER -