PMID- 38020809
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 2665-945X (Electronic)
IS  - 2665-945X (Linking)
VI  - 5
DP  - 2023
TI  - From X-inactivation to neurodevelopment: CHD8-transcription factors (TFs) 
      competitive binding at regulatory regions of CHD8 target genes can contribute to 
      correct neuronal differentiation.
PG  - 100114
LID - 10.1016/j.crneur.2023.100114 [doi]
LID - 100114
AB  - The chromodomain helicase DNA-binding protein 8 (CHD8) is a chromatin remodeler 
      whose mutation is associated, with high penetrance, with autism. Individuals with 
      CHD8 mutations share common symptoms such as autistic behaviour, cognitive 
      impairment, schizophrenia comorbidity, and phenotypic features such as 
      macrocephaly and facial defects. Chd8-deficient mouse models recapitulate most of 
      the phenotypes seen in the brain and other organs of humans. It is known that 
      CHD8 regulates - directly and indirectly - neuronal, autism spectrum disorder 
      (ASDs)-associated genes and long non-coding RNAs (lncRNAs) genes, which, in turn, 
      regulate fundamental aspects of neuronal differentiation and brain development 
      and function. A major characteristic of CHD8 regulation of gene expression is its 
      non-linear and dosage-sensitive nature. CHD8 mutations appear to affect males 
      predominantly, although the reasons for this observed sex bias remain- unknown. 
      We have recently reported that CHD8 directly regulates X chromosome inactivation 
      (XCI) through the transcriptional control of the Xist long non-coding RNA 
      (lncRNA), the master regulator of mammalian XCI. We identified a role for CHD8 in 
      regulating accessibility at the Xist promoter through competitive binding with 
      transcription factors (TFs) at Xist regulatory regions. We speculate here that 
      CHD8 might also regulate accessibility at neuronal/ASD targets through a similar 
      competitive binding mechanism during neurogenesis and brain development. However, 
      whilst such a model can reconcile the phenotypic differences observed in Chd8 
      knock-down (KD) vs knock-out (KO) mouse models, explaining the observed CHD8 
      non-linear dosage-dependent activity, it cannot on its own explain the observed 
      disease sex bias.
CI  - (c) 2023 The Authors.
FAU - Cerase, Andrea
AU  - Cerase A
AD  - Department of Biology, University of Pisa, Italy.
FAU - Avner, Philip
AU  - Avner P
AD  - EMBL Rome, Via Ramarini 32, Monterotondo, 00015, RM, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20231107
PL  - Netherlands
TA  - Curr Res Neurobiol
JT  - Current research in neurobiology
JID - 101778135
PMC - PMC10663126
OTO - NOTNLM
OT  - Chromatin remodeler
OT  - Chromodomain helicase DNA-Binding protein 8 (CHD8)
OT  - Competitive binding
OT  - Dosage sensitive gene regulation
OT  - Long non-coding RNA
OT  - Non-linear gene regulation
OT  - Sex bias
OT  - Transcription factors (TFs)
OT  - X-inactive specific transcript (Xist)
OT  - Yin Yang 1 (YY1)
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2023/11/29 18:43
MHDA- 2023/11/29 18:44
PMCR- 2023/11/07
CRDT- 2023/11/29 14:51
PHST- 2023/04/17 00:00 [received]
PHST- 2023/09/19 00:00 [revised]
PHST- 2023/10/15 00:00 [accepted]
PHST- 2023/11/29 18:44 [medline]
PHST- 2023/11/29 18:43 [pubmed]
PHST- 2023/11/29 14:51 [entrez]
PHST- 2023/11/07 00:00 [pmc-release]
AID - S2665-945X(23)00042-6 [pii]
AID - 100114 [pii]
AID - 10.1016/j.crneur.2023.100114 [doi]
PST - epublish
SO  - Curr Res Neurobiol. 2023 Nov 7;5:100114. doi: 10.1016/j.crneur.2023.100114. 
      eCollection 2023.