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Series GSE164360 Query DataSets for GSE164360
Status Public on Apr 07, 2021
Title Epigenomic Activation of Enhancers in Granule Cell Precursors by CHARGE Syndrome Protein CHD7 Regulates Gyrification of the Mammalian Cerebellum
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Regulation of chromatin plays fundamental roles in the normal development of the brain. Haploinsufficiency of the chromatin remodeling enzyme CHD7 causes CHARGE syndrome, a genetic disorder that prominently affects the development of the cerebellum. However, how CHD7 controls chromatin states in the cerebellum remains incompletely understood. Using conditional knockout of CHD7 in granule cell precursors in the mouse cerebellum, we find that CHD7 robustly promotes the accessibility and activity of enhancers in granule cell precursors. Remarkably, in vivo profiling of genome architecture reveals that CHD7 operates locally to stimulate enhancer activation, thereby driving the expression of topologically-interacting genes. Genome and gene ontology studies show that CHD7-regulated enhancers are associated prominently with genes that control brain tissue morphogenesis. Accordingly, conditional knockout of CHD7 triggers a striking phenotype of cerebellar polymicrogyria, which we have also found in a case of CHARGE syndrome. Finally, we uncover a CHD7-dependent switch in the preferred orientation of granule cell precursor division in the developing cerebellum, providing a cellular basis for the cerebellar polymicrogyria phenotype upon loss of CHD7. Collectively, our findings define CHD7 function in the regulation of the epigenome in granule cell precursors and identify a surprising link of CHD7 to the control of cerebellar cortical morphogenesis, with potential implications for our understanding of CHARGE syndrome.
Overall design Examination of the role of CHD7 to regulate the epigenome and cerebellar folding in control and conditional knockout mice.
Contributor(s) Reddy NC, Majidi SP, Kong L, Nemera M, Ferguson CJ, Moore M, Goncalves TM, Liu H, Fitzpatrick JA, Zhao G, Yamada T, Bonni A, Gabel HW
Citation(s) 34588434
Submission date Jan 06, 2021
Last update date Oct 27, 2021
Contact name Naveen Reddy
Organization name Washington University In St. Louis
Street address 660 S Euclid Ave
City st. louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (104)
GSM5008188 P4_ChIP_CTCF_cKO_1
GSM5008189 P4_ChIP_CTCF_cKO_2
GSM5008190 P4_ChIP_CTCF_cKO_3
BioProject PRJNA690106
SRA SRP300663

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

Supplementary file Size Download File type/resource
GSE164360_ATAC_Peaks.bed.gz 1.4 Mb (ftp)(http) BED
GSE164360_CHD7_Peaks.bed.gz 255.0 Kb (ftp)(http) BED
GSE164360_CTCF_Peaks.bed.gz 694.0 Kb (ftp)(http) BED
GSE164360_H3K27ac_Peaks.bed.gz 308.2 Kb (ftp)(http) BED
GSE164360_H3K4me1_Peaks.bed.txt.gz 1.1 Mb (ftp)(http) TXT
GSE164360_H3K4me3_Peaks.bed.txt.gz 333.9 Kb (ftp)(http) TXT
GSE164360_Hi-C_Summary.xlsx 1.1 Mb (ftp)(http) XLSX
GSE164360_RAD21_Peaks.bed.gz 618.6 Kb (ftp)(http) BED
GSE164360_RNA-seq_Summary.xlsx 3.7 Mb (ftp)(http) XLSX
GSE164360_RNApolII_Peaks.bed.gz 430.0 Kb (ftp)(http) BED
GSE164360_RNApolII_Peaks.bed.txt.gz 430.0 Kb (ftp)(http) TXT
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