Biology subjects

Ben-Tov Perry, R.

Publications and source records attributed to Ben-Tov Perry, R..

3 recordsLinked to original sources

bioRxiv2025

BAHCC1 promotes gene expression in neuronal cells by antagonizing SIN3A-HDAC1

Chromatin modifications play a key role in regulating gene expression during development and adult physiology. Histone acetylation, particularly H3K27ac, is associated with increased activity of gene regulatory elements such as enhancers and promoters. However, the regulation of the machinery that write, read, and erase this modification remains poorly understood. In particular, the SIN3A-HDAC1 complex possesses histone deacetylase activity, yet it commonly resides at active regulatory regions. Here, we study BAHCC1, a large chromatin-associated protein essential for viability, and recently reported to play a largely repressive role. We show that in neuronal lineage cells, BAHCC1 is mainly associated with regulatory elements marked with H3K27ac. BAHCC1 interacts and co-occupies shared genomic regions with the SIN3A scaffold protein, and its perturbations lead to altered acetylation and expression of proximal genes in a neuronal cell line and primary cortical neurons. The regulated genes are enriched for those functioning in neurogenesis and cell migration, and primary cortical neurons with reduced Bahcc1 expression display impaired neurite outgrowth. We thus propose a model in which BAHCC1 antagonizes SIN3A histone deacetylation and positively regulates the expression of genes that are important for growth and migration-related processes in the neuronal lineage.

molecular biology↗

bioRxiv2022

Silc1 long noncoding RNA is an immediate-early gene promoting efficient memory formation

Long noncoding RNAs (lncRNAs) are expressed in many brain circuits and neuronal types, but their significance to normal brain functions has remained largely unknown. Here, we study the functions in the central nervous system of Silc1, a lncRNA we previously showed to be important for neuroregeneration in the peripheral nervous system. We found that Silc1 is rapidly and strongly induced upon stimulation in the hippocampus and is required for efficient spatial learning. Silc1 production is important for the induction of Sox11 (its cis-regulated target gene) throughout the CA1-CA3 regions and the proper expression of key Sox11 target genes. Consistent with its newly found role in neuronal plasticity, we find that during aging and in models of Alzheimers disease Silc1 levels decline. Overall, we uncover a novel plasticity pathway, in which Silc1 acts as an immediate-early gene to activate Sox11 to induce a neuronal growth-associated transcriptional program important for memory formation.

molecular biology↗

bioRxiv2019

Regulation of CHD2 expression by the Chaserr long noncoding RNA is essential for viability

Genomic loci adjacent to genes encoding for transcription factors and chromatin remodelers are enriched for long non-coding RNAs (lncRNAs), but the functional importance of this enrichment is largely unclear. Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller with various reported functions in cell differentiation and DNA damage response. Heterozygous mutations in human CHD2 have been implicated in epilepsy, neurodevelopmental delay, and intellectual disability. Here we show that Chaserr, a highly conserved lncRNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to increased transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potentially viable strategy for increasing CHD2 levels in haploinsufficient individuals.

molecular biology↗