Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.
Accurate read-out of chromatin modifications is essential for eukaryotic life. Mutations in the gene encoding X-linked ATRX protein cause a mental-retardation syndrome, whereas wild-type ATRX protein targets pericentric and telomeric heterochromatin for deposition of the histone variant H3.3 by mean...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2011
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| _version_ | 1826269995073536000 |
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| author | Eustermann, S Yang, J Law, M Amos, R Chapman, L Jelinska, C Garrick, D Clynes, D Gibbons, R Rhodes, D Higgs, D Neuhaus, D |
| author_facet | Eustermann, S Yang, J Law, M Amos, R Chapman, L Jelinska, C Garrick, D Clynes, D Gibbons, R Rhodes, D Higgs, D Neuhaus, D |
| author_sort | Eustermann, S |
| collection | OXFORD |
| description | Accurate read-out of chromatin modifications is essential for eukaryotic life. Mutations in the gene encoding X-linked ATRX protein cause a mental-retardation syndrome, whereas wild-type ATRX protein targets pericentric and telomeric heterochromatin for deposition of the histone variant H3.3 by means of a largely unknown mechanism. Here we show that the ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. In vivo experiments show this combinatorial readout is required for ATRX localization, with recruitment enhanced by a third interaction through heterochromatin protein-1 (HP1) that also recognizes trimethylated Lys9. The cooperation of ATRX ADD domain and HP1 in chromatin recruitment results in a tripartite interaction that may span neighboring nucleosomes and illustrates how the 'histone-code' is interpreted by a combination of multivalent effector-chromatin interactions. |
| first_indexed | 2024-03-06T21:33:56Z |
| format | Journal article |
| id | oxford-uuid:459acf87-ea9b-4026-a3bb-ec4fe14dff56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:33:56Z |
| publishDate | 2011 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:459acf87-ea9b-4026-a3bb-ec4fe14dff562022-03-26T15:08:42ZCombinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:459acf87-ea9b-4026-a3bb-ec4fe14dff56EnglishSymplectic Elements at OxfordNature Publishing Group2011Eustermann, SYang, JLaw, MAmos, RChapman, LJelinska, CGarrick, DClynes, DGibbons, RRhodes, DHiggs, DNeuhaus, DAccurate read-out of chromatin modifications is essential for eukaryotic life. Mutations in the gene encoding X-linked ATRX protein cause a mental-retardation syndrome, whereas wild-type ATRX protein targets pericentric and telomeric heterochromatin for deposition of the histone variant H3.3 by means of a largely unknown mechanism. Here we show that the ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. In vivo experiments show this combinatorial readout is required for ATRX localization, with recruitment enhanced by a third interaction through heterochromatin protein-1 (HP1) that also recognizes trimethylated Lys9. The cooperation of ATRX ADD domain and HP1 in chromatin recruitment results in a tripartite interaction that may span neighboring nucleosomes and illustrates how the 'histone-code' is interpreted by a combination of multivalent effector-chromatin interactions. |
| spellingShingle | Eustermann, S Yang, J Law, M Amos, R Chapman, L Jelinska, C Garrick, D Clynes, D Gibbons, R Rhodes, D Higgs, D Neuhaus, D Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title | Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title_full | Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title_fullStr | Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title_full_unstemmed | Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title_short | Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. |
| title_sort | combinatorial readout of histone h3 modifications specifies localization of atrx to heterochromatin |
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