@article{ae207533109b4fc88632b4a7d236fd9c,
title = "The epigenetic reader PHF21B modulates murine social memory and synaptic plasticity–related genes",
abstract = "Synaptic dysfunction is a manifestation of several neurobehavioral and neurological disorders. A major therapeutic challenge lies in uncovering the upstream regulatory factors controlling synaptic processes. Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological disorders. However, the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here, we generated a PHD finger protein 21B–depleted (Phf21bdepleted) mutant CRISPR mouse model (hereafter called Phf21bΔ4/Δ4) to examine Phf21b{\textquoteright}s roles in the brain. Phf21bΔ4/Δ4 animals exhibited impaired social memory. In addition, reduced expression of synaptic proteins and impaired long-term potentiation were observed in the Phf21bΔ4/Δ4 hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a potentially novel interaction of PHF21B with histone H3 trimethylated lysine 36 (H3K36me3), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity–related genes and a candidate therapeutic target for neurobehavioral dysfunction in mice, with potential applications in human neurological and psychiatric disorders.",
author = "Chin, {Eunice W.M.} and Qi Ma and Hongyu Ruan and Camille Chin and Aditya Somasundaram and Chunling Zhang and Chunyu Liu and Lewis, {Martin D.} and Melissa White and Smith, {Tracey L.} and Malcolm Battersby and Yao, {Wei Dong} and Lu, {Xin Yun} and Wadih Arap and Julio Licinio and Wong, {Ma Li}",
note = "Funding Information: The authors thank Jianhua Chen and Rhys Fogarty for their technical assistance and animal colony maintenance and the State University of New York Molecular Analysis Core Facility for help with RNA-Seq experiments. The dorsal mouse hippocampus schematic in the graphical abstract was created with a CC-BY license from https://doi.org/10.6084/m9.figshare.5027348.v3. This work was supported by National Health and Medical Council (Australia) grants APP105193 (to MLW) and APP1145770 (to MB, JL, and MLW); NIH grants R21MH126405 (to JL and MLW), R21MH128726 (to JL and MLW), and R01MH127423 (to JL and MLW); State University of New York Upstate Medical University institutional funds (to MLW); South Australian Health and Medical Research Institute institutional funds (to MB, JL, and MLW); and an award from the Longenbaugh-Levy Donor-Advised Fund (to WA). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2022, Chin et al.",
year = "2022",
month = jul,
day = "22",
doi = "10.1172/jci.insight.158081",
language = "English",
volume = "7",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "14",
}