NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE98477 Query DataSets for GSE98477
Status Public on May 19, 2017
Title YY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunction [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth retardation, feeding problems, and various congenital malformations. Our combined clinical and molecular data define the ‘YY1 syndrome’ as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from person-derived cells, using antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding, with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators.
 
Overall design Individuals with mutations or deletion in YY1 were identified among patients with idiopathic intellectual disability. LCLs were established from 4 of these patients (1 deletion, 2 missense mutations, and 1 non-sense mutation undergoing non-sense-mediated decay) and from unrelated controls. These lines were profiled for genome-wide YY1 occupancy using two antibodies respectively binding each end of the protein, as well as for H3K27ac and H3K27me3.
 
Contributor(s) Gabriele M, Silfhout AT, Germain P, Vitriolo A, Kumar R, Gecz J, Koolen DA, Testa G, de Vries BB
Citation(s) 28575647
Submission date May 02, 2017
Last update date Jul 25, 2021
Contact name Giuseppe Testa
E-mail(s) giuseppe.testa@ieo.it
Organization name European Institute of Oncology & University of Milano, Italy
Lab Neurogenomics Research Centre
Street address Via Adamello, 16
City Milano
ZIP/Postal code 20139
Country Italy
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (38)
GSM2597204 H3K27Ac ChIPseq in CTRL1_AB LCLs
GSM2597205 H3K27Ac ChIPseq in CTRL2_BH LCLs
GSM2597206 H3K27Ac ChIPseq in CTRL3_JD LCLs
This SubSeries is part of SuperSeries:
GSE98478 YY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunction.
Relations
BioProject PRJNA385187
SRA SRP106078

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
GSE98477_RAW.tar 22.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap