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| Status |
Public on Aug 31, 2017 |
| Title |
Structural and mechanistic insights into ATRX-dependent and –independent functions of the histone chaperone DAXX [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The histone variant H3.3 is incorporated in a replication-independent manner at heterochromatic regions by the ATRX-DAXX histone chaperone complex. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We used single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and -independent functions of DAXX. We found that  the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: The ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We found that histone H3.3 stabilizes DAXX protein levels and affects DAXX-regulated genes independently of its incorporation into nucleosomes. Our findings represent the first description of a nucleosome-independent function for the H3.3 histone variant.
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| Overall design |
RNA-seq analysis of five embryonic stem cell lines in duplicate (Daxx-/- mESC, Daxx-/- mESC rescued with Daxx WT, H3.3 KO mESC, H3.3 KO mESC rescued with H3.3 WT and H3.3 L126A-L130A mutant)
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| Contributor(s) |
Lewis PW, Hoelper D, Jain AY |
| Citation(s) |
29084956 |
| |
| Submission date |
Aug 15, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter W Lewis |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Wisconsin-Madison
|
| Department |
Department of Biomolecular Chemistry
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| Lab |
Department of Biomolecular Chemistry
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| Street address |
330 N Orchard Street
|
| City |
Madison |
| State/province |
Wisconsin |
| ZIP/Postal code |
53715 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA398383 |
| SRA |
SRP115486 |
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