PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex

Stephanie Link; Ramona M M Spitzer; Maryam Sana; Mario Torrado; Moritz C Völker-Albert; Eva C Keilhauer; Thomas Burgold; Sebastian Pünzeler; Jason K K Low; Ida Lindström; Andrea Nist; Catherine Regnard; Thorsten Stiewe; Brian Hendrich; Axel Imhof; Matthias Mann; Joel P Mackay; Marek Bartkuhn; Sandra B Hake

doi:10.1038/s41467-018-06665-5

PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex

Stephanie Link, Ramona M M Spitzer, Maryam Sana, Mario Torrado, Moritz C Völker-Albert, Eva C Keilhauer, Thomas Burgold, Sebastian Pünzeler, Jason K K Low, Ida Lindström, Andrea Nist, Catherine Regnard, Thorsten Stiewe, Brian Hendrich, Axel Imhof, Matthias Mann, Joel P Mackay, Marek Bartkuhn, Sandra B Hake

12 Citations (Scopus)

Abstract

Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.

Original language	English
Journal	Nature Communications
Volume	9
Issue number	1
Pages (from-to)	4300
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-06665-5
Publication status	Published - 1 Dec 2018
Externally published	Yes

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Link, S., Spitzer, R. M. M., Sana, M., Torrado, M., Völker-Albert, M. C., Keilhauer, E. C., Burgold, T., Pünzeler, S., Low, J. K. K., Lindström, I., Nist, A., Regnard, C., Stiewe, T., Hendrich, B., Imhof, A., Mann, M., Mackay, J. P., Bartkuhn, M., & Hake, S. B. (2018). PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex. Nature Communications, 9(1), 4300. https://doi.org/10.1038/s41467-018-06665-5

Link, S, Spitzer, RMM, Sana, M, Torrado, M, Völker-Albert, MC, Keilhauer, EC, Burgold, T, Pünzeler, S, Low, JKK, Lindström, I, Nist, A, Regnard, C, Stiewe, T, Hendrich, B, Imhof, A, Mann, M, Mackay, JP, Bartkuhn, M & Hake, SB 2018, 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex', Nature Communications, vol. 9, no. 1, pp. 4300. https://doi.org/10.1038/s41467-018-06665-5

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title = "PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex",

abstract = "Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.",

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AU - Link, Stephanie

AU - Spitzer, Ramona M M

AU - Sana, Maryam

AU - Torrado, Mario

AU - Völker-Albert, Moritz C

AU - Keilhauer, Eva C

AU - Burgold, Thomas

AU - Pünzeler, Sebastian

AU - Low, Jason K K

AU - Lindström, Ida

AU - Nist, Andrea

AU - Regnard, Catherine

AU - Stiewe, Thorsten

AU - Hendrich, Brian

AU - Imhof, Axel

AU - Mann, Matthias

AU - Mackay, Joel P

AU - Bartkuhn, Marek

AU - Hake, Sandra B

PY - 2018/12/1

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N2 - Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.

AB - Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.

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JO - Nature Communications

JF - Nature Communications

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PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex

Abstract

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