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Series GSE102688 Query DataSets for GSE102688
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.
 
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)
 
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) pwlewis2@wisc.edu
Organization name University of Wisconsin-Madison
Department Department of Biomolecular Chemistry
Lab Department of Biomolecular Chemistry
Street address 330 N Orchard Street
City Madison
State/province Wisconsin
ZIP/Postal code 53715
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (10)
GSM2742944 DaxxKO rep1
GSM2742945 DaxxKO rep2
GSM2742946 DaxxWT rep1
Relations
BioProject PRJNA398383
SRA SRP115486

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE102688_TPM_Daxx_H3.3.txt.gz 438.1 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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