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Genome-wide maps of gene transcription and chromatin state in mouse Setdb1 wildtype and CK-cre conditional knockout brain.

ABSTRACT: We report locus-specific disintegration of megabase-scale chromosomal conformations after Kmt1e/Setdb1 histone H3-lysine 9 methyltransferase ablation in mouse brian. Histone modification, CCCTC-binding factor (CTCF), transcriptome and ‘3D genome’ (in situ Hi-C) mappings each identified a uniquely affected ~1Mb domain on chromosome 18 in cortical and striatal neurons, encompassing the Protocadherin cell adhesion gene clusters (cPcdh). Setdb1-deficient neuronal genomes showed de novo CTCF occupancies at thousands of cryptic binding sites and locus-specific disintegration of 1Mb cPcdh higher order chromatin. Loss of long-range repressive chromosomal conformations triggered massively increased proportions of neurons expressing specific cPcdh genes due to relaxation of stochastic constraint. Setdb1, shielding mature neuronal genomes from excess CTCF binding, maintains TAD integrity essential for mouse brain function.

ORGANISM(S): Mus musculus

PROVIDER: GSE99363 | GEO | 2017/07/01

SECONDARY ACCESSION(S): PRJNA388197

REPOSITORIES: GEO

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