ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner

Martin Law; Karen Lower; Hsiao Voon; Jim Hughes; David Garrick; Vip Viprakasit; Matthew Mitson; Marco De Gobbi; Marco Marra; Andrew Morris; Aaron Abbott; Steven Wilder; Stephen Taylor; Guilherme Santos; Joe Cross; Helena Ayyub; Steven Jones; Jiannis Ragoussis; Daniela Rhodes; Ian Dunham; Doug Higgs; Richard Gibbons

doi:10.1016/j.cell.2010.09.023

ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner

Martin Law, Karen Lower, Hsiao Voon, Jim Hughes, David Garrick, Vip Viprakasit, Matthew Mitson, Marco De Gobbi, Marco Marra, Andrew Morris, Aaron Abbott, Steven Wilder, Stephen Taylor, Guilherme Santos, Joe Cross, Helena Ayyub, Steven Jones, Jiannis Ragoussis, Daniela Rhodes, Ian DunhamDoug Higgs, Richard Gibbons

Research output: Contribution to journal › Article › peer-review

335 Citations (Scopus)

Abstract

ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.

Original language	English
Pages (from-to)	367-378
Number of pages	12
Journal	Cell
Volume	143
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2010.09.023
Publication status	Published - 29 Oct 2010

Keywords

DNA
HUMDISEASE
PROTEINS

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10.1016/j.cell.2010.09.023

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Law, M., Lower, K., Voon, H., Hughes, J., Garrick, D., Viprakasit, V., Mitson, M., De Gobbi, M., Marra, M., Morris, A., Abbott, A., Wilder, S., Taylor, S., Santos, G., Cross, J., Ayyub, H., Jones, S., Ragoussis, J., Rhodes, D., ... Gibbons, R. (2010). ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner. Cell, 143(3), 367-378. https://doi.org/10.1016/j.cell.2010.09.023

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title = "ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner",

abstract = "ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.",

keywords = "DNA, HUMDISEASE, PROTEINS",

author = "Martin Law and Karen Lower and Hsiao Voon and Jim Hughes and David Garrick and Vip Viprakasit and Matthew Mitson and {De Gobbi}, Marco and Marco Marra and Andrew Morris and Aaron Abbott and Steven Wilder and Stephen Taylor and Guilherme Santos and Joe Cross and Helena Ayyub and Steven Jones and Jiannis Ragoussis and Daniela Rhodes and Ian Dunham and Doug Higgs and Richard Gibbons",

year = "2010",

month = oct,

day = "29",

doi = "10.1016/j.cell.2010.09.023",

language = "English",

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Law, M, Lower, K, Voon, H, Hughes, J, Garrick, D, Viprakasit, V, Mitson, M, De Gobbi, M, Marra, M, Morris, A, Abbott, A, Wilder, S, Taylor, S, Santos, G, Cross, J, Ayyub, H, Jones, S, Ragoussis, J, Rhodes, D, Dunham, I, Higgs, D & Gibbons, R 2010, 'ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner', Cell, vol. 143, no. 3, pp. 367-378. https://doi.org/10.1016/j.cell.2010.09.023

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T1 - ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner

AU - Law, Martin

AU - Lower, Karen

AU - Voon, Hsiao

AU - Hughes, Jim

AU - Garrick, David

AU - Viprakasit, Vip

AU - Mitson, Matthew

AU - De Gobbi, Marco

AU - Marra, Marco

AU - Morris, Andrew

AU - Abbott, Aaron

AU - Wilder, Steven

AU - Taylor, Stephen

AU - Santos, Guilherme

AU - Cross, Joe

AU - Ayyub, Helena

AU - Jones, Steven

AU - Ragoussis, Jiannis

AU - Rhodes, Daniela

AU - Dunham, Ian

AU - Higgs, Doug

AU - Gibbons, Richard

PY - 2010/10/29

Y1 - 2010/10/29

N2 - ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.

AB - ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.

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KW - HUMDISEASE

KW - PROTEINS

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U2 - 10.1016/j.cell.2010.09.023

DO - 10.1016/j.cell.2010.09.023

M3 - Article

SN - 0092-8674

VL - 143

SP - 367

EP - 378

JO - Cell

JF - Cell

IS - 3

ER -

ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner

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Keywords

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