Table 1.
NuRD’s role in brain development and neuronal plasticity.
| Reference | Species | Model | Tissue | Region/cell type | Major technique | Major findings |
|---|---|---|---|---|---|---|
| (Yamada et al., 2014) | r, m | in vivo RNAi, conditional Chd4 knock-out | cerebellum | cerebellar cortex/granule neurons | RNA-seq/ChIP-seq, WCPC, EM | NuRD supports the development of granule neuron parallel fiber/Purkinje cell synapse by repressing inhibitors of presynaptic connectivity during critical post-natal time windows of plasticity. |
| (Yang et al., 2016) | m | conditional Chd4 knock-out, in vivo transfection, behavioral tests | cerebellum | cerebellar cortex | RNA-seq/ChIP-seq, Ca2+ imaging, histology | NuRD inhibits expression of active genes by deposition of the histone variant H2A.z. Thereby, NuRD controls deactivation of neuronal-activity dependent gene transcription, reduces neuronal pruning during sensitive periods, and regulates behavioral responses. |
| (Knock et al., 2015) | m | conditional Mbd3 knock-out | developing neocortex | apical and basal progenitors | IHC, ChIP, microarray, qRT-PCR | NuRD/Mbd3 sustains appropriate cell lineage choice and differentiation programs by terminating pro-neurogenic transcription in both progenitor cells and neuronal progeny. |
| (Egan et al., 2013) | m, h | in utero electro-poration | developing neocortex | developing neocortex, ESCs, neuroblastoma | shRNA, IHC, microarray, ChIP-Seq | Chd5 facilitates activation of neuronal gene expression and maintains repression of a small cohort of Polycomb repressed genes during embryonic neocortex development. |
| (Potts et al., 2011) | r | primary neuronal culture | developing cortex | cortex, post-mitotic neurons | shRNA, IHC, Co-IP, ChiP, microarray | Chd5 regulates neuronal genes and chromatin modifiers in embryonic neurons. NuRD/Chd5 also strongly regulates genes associated with aging and Alzheimer’s disease. |
| (Nitarska et al., 2016) | m | chd4 knock-out, in utero electro-poration | developing cortex | progenitors, early and late migrating neurons | IHC, mass spectrometry, microarray, ChIP | Chd3, Chd4, and Chd5 are mutually exclusive NuRD subunits during corticogenesis and regulate distinct set of genes; Chd4 promotes basal progenitor proliferation, Chd5 drives early radial migration, and Chd3 facilitates late migration and laminar specification. |
| (Muralidharan et al., 2017) | m | Lhx2 knock-out, in utero electro-poration | developing cortex | deep layer 5 and 6, superficial layer 2 and 3 | IHC, ISH, mass spectrometry, ChIP-seq/-PCR | Lhx2-null mice show more layer 5 neurons with high Fezf2/Ctip2 expression, while layer 6 neurons with Tbr-1 expression are less. Lxh2 regulates layer subtype specificity through enhanced recruitment of NuRD repressor activity to Fezh2, and its activator Sox11. |
| (Topark-Ngarm et al., 2006) | h | human neuroblastoma | transfections, chromatography, microarray | CTIP2 associates with NuRD on the promoter of p57KIP2 and confers repression. shRNA-mediated knockdown of CTIP enhances p57KIP2 expression. | ||
| (Harb et al., 2016) | m | Lmo4 or Nr2f1 knock-out, in utero electro-poration | postnatal cortex | somatosensory cortex, layer 5 projection neurons | IHC, ISH, ChIP, Co-IP, retrograde labeling | Ctip2/Satb2 co-expression defines two distinct subtypes of postnatal projection neurons. Thereby, Lmo4 targets Satb2/NuRD at Ctip2 and prevents Hdac1-mediated histone deacetylation. |
ChIP, chromatin immunoprecipitation; ChIP-seq, chromatin immunoprecipitation sequencing; Co-IP, coimmunoprecipitation; EM, electron microcopy; IHC, immunohistochemistry; ISH, in situ hybridization; qRT-PCR, quantitative reverse transcribed polymerase chain reaction; RNA-seq, RNA sequencing; shRNA, short hairpin RNA; WCPC, whole-cell patch clamp.