PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex
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PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex. / Todd, Matthew A.M.; Picketts, David J.
In: Journal of Proteome Research, Vol. 11, No. 8, 03.08.2012, p. 4326-4337.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex
AU - Todd, Matthew A.M.
AU - Picketts, David J.
PY - 2012/8/3
Y1 - 2012/8/3
N2 - Mutations in PHF6 are the cause of Börjeson-Forssman-Lehman syndrome (BFLS), an X-linked intellectual disability (XLID) disorder, and both T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). The PHF6 gene encodes a protein with two plant homeodomain (PHD)-like zinc finger domains. As many PHD-like domains function to target chromatin remodelers to post-translationally modified histones, this suggests a role for PHF6 in chromatin regulation. However, PHD domains are usually found in association with a catalytic domain, a feature that is lacking in PHF6. This distinct domain structure and the minimal information on its cellular function prompted us to perform a proteomic screen to identify PHF6 binding partners. We expressed recombinant Flag-tagged PHF6 in HEK 293T cells for coimmunoprecipitation, and analyzed the purified products by mass spectrometry. We identified proteins involved in ribosome biogenesis, RNA splicing, and chromatin regulation, consistent with PHF6 localization to both the nucleoplasm and nucleolus. Notably, PHF6 copurified with multiple constituents of the nucleosome remodeling and deacetylation (NuRD) complex, including CHD4, HDAC1, and RBBP4. We demonstrate that this PHF6-NuRD complex is not present in the nucleolus but is restricted to the nucleoplasm. The association with NuRD represents the first known interaction for PHF6 and implicates it in chromatin regulation.
AB - Mutations in PHF6 are the cause of Börjeson-Forssman-Lehman syndrome (BFLS), an X-linked intellectual disability (XLID) disorder, and both T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). The PHF6 gene encodes a protein with two plant homeodomain (PHD)-like zinc finger domains. As many PHD-like domains function to target chromatin remodelers to post-translationally modified histones, this suggests a role for PHF6 in chromatin regulation. However, PHD domains are usually found in association with a catalytic domain, a feature that is lacking in PHF6. This distinct domain structure and the minimal information on its cellular function prompted us to perform a proteomic screen to identify PHF6 binding partners. We expressed recombinant Flag-tagged PHF6 in HEK 293T cells for coimmunoprecipitation, and analyzed the purified products by mass spectrometry. We identified proteins involved in ribosome biogenesis, RNA splicing, and chromatin regulation, consistent with PHF6 localization to both the nucleoplasm and nucleolus. Notably, PHF6 copurified with multiple constituents of the nucleosome remodeling and deacetylation (NuRD) complex, including CHD4, HDAC1, and RBBP4. We demonstrate that this PHF6-NuRD complex is not present in the nucleolus but is restricted to the nucleoplasm. The association with NuRD represents the first known interaction for PHF6 and implicates it in chromatin regulation.
KW - AML
KW - BFLS
KW - NuRD
KW - PHF6
KW - protein-protein interaction
KW - T-ALL
KW - XLID
UR - http://www.scopus.com/inward/record.url?scp=84864627629&partnerID=8YFLogxK
U2 - 10.1021/pr3004369
DO - 10.1021/pr3004369
M3 - Journal article
C2 - 22720776
AN - SCOPUS:84864627629
VL - 11
SP - 4326
EP - 4337
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 8
ER -
ID: 319873873