• Molecules and Cells
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• v.44 no.11
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• pp.805-829
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• 2021

CCCTC-binding factor (CTCF) critically contributes to 3D chromatin organization by determining topologically associated domain (TAD) borders. Although CTCF primarily binds at TAD borders, there also exist putative CTCF-binding sites within TADs, which are spread throughout the genome by retrotransposition. However, the detailed mechanism responsible for masking the putative CTCF-binding sites remains largely elusive. Here, we show that the ATP-dependent chromatin remodeler, chromodomain helicase DNA-binding 4 (CHD4), regulates chromatin accessibility to conceal aberrant CTCF-binding sites embedded in H3K9me3-enriched heterochromatic B2 short interspersed nuclear elements (SINEs) in mouse embryonic stem cells (mESCs). Upon CHD4 depletion, these aberrant CTCF-binding sites become accessible and aberrant CTCF recruitment occurs within TADs, resulting in disorganization of local TADs. RNA-binding intrinsically disordered domains (IDRs) of CHD4 are required to prevent this aberrant CTCF binding, and CHD4 is critical for the repression of B2 SINE transcripts. These results collectively reveal that a CHD4-mediated mechanism ensures appropriate CTCF binding and associated TAD organization in mESCs.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.111-114
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• 2022

Many monogenic neurodevelopmental disorders have been newly identified in recent years owing to the rapid development of genetic sequencing technology. These include variants of the epigenetic machinery - up to 300 known epigenetic factors of which about 50 have been linked to specific clinical phenotypes. Chromodomain, helicase, DNA binding 1 (CHD1) is an ATP-dependent chromatin remodeler, known to be the causative gene of the autosomal dominant neurodevelopmental disorder Pilarowski-Bjornsson syndrome. Patients exhibit various degrees of global developmental delay, autism, speech apraxia, seizures, growth retardation, and craniofacial dysmorphism. We report the first case of Pilarowski-Bjornsson syndrome in Korea, due to a de novo missense variant of the CHD1 gene (c.862A>G, p.Thr288Ala) in a previously undiagnosed 17-year-old male. His infantile onset of severe global developmental delay, intellectual disability, speech apraxia, and failure to thrive are compatible with Pilarowski-Bjornsson syndrome. We also noted some features not previously reported in this syndrome such as skeletal dysplasia and ichthyosis. Further studies are needed to discover the specific phenotypes and pathogenic mechanisms behind this rare disorder.