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| 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
Other
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| 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.
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| Overall design |
Examination of the role of CHD7 to regulate the epigenome and cerebellar folding in control and conditional knockout mice.
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| 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 |
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| Submission date |
Jan 06, 2021 |
| Last update date |
Oct 27, 2021 |
| Contact name |
Naveen Reddy |
| Organization name |
Washington University In St. Louis
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| Street address |
660 S Euclid Ave
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| City |
st. louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (104)
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| Relations |
| BioProject |
PRJNA690106 |
| SRA |
SRP300663 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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