Biology subjects

Kaurani, L.

Publications and source records attributed to Kaurani, L..

3 recordsLinked to original sources

bioRxiv2021

H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion by activating TRNP1 expression

Increase in the size of human neocortex, acquired in evolution, accounts for the unique cognitive capacity of humans. This expansion appears to reflect the evolutionarily-enhanced proliferative ability of basal progenitors (BPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, whether or how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in BP amplification and cortical expansion. Through epigenetic profiling of sorted BPs, we show that H3K9 acetylation is low in murine BPs and high in human BPs. Elevated H3K9ac preferentially increases BP proliferation, increasing the size and folding of the normally smooth mouse neocortex. Mechanistically, H3K9ac drives BP amplification by increasing expression of the evolutionarily regulated gene, TRNP1, in the developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture. One Sentence SummaryH3K9ac promotes basal progenitor amplification, neocortex expansion and gyrification by activating TRNP1 expression in evolution.

developmental biology↗

bioRxiv2020

Integrated multi-omics analysis reveals common and distinct dysregulated pathways for genetic subtypes of Frontotemporal Dementia

Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, and small RNA-seq, and supplemented this date with CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.

neuroscience↗

bioRxiv2020

SETD1B controls cognitive function via cell type specific regulation of neuronal identity genes

Histone-3-lysine-4-methylation (H3K4me) is mediated by six different lysine methyltransferases (KMTs). Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to intellectual disability but its role in the adult brain has not been studied yet. Here we show that mice lacking Setd1b from excitatory neurons of the adult forebrain exhibit severe memory impairment. By combining neuron-specific ChIP-seq, RNA-seq and single cell RNA-seq approaches we show that Setd1b controls the expression of neuronal-identity genes with a broad H3K4me3 peak linked to learning and memory processes. Our data furthermore suggest that basal neuronal gene-expression is ensured by other H3K4 KMTs such as Kmt2a and Kmt2b while the additional presence of Setd1b at the single cell level provides transcriptional consistency to the expression of genes important for learning & memory.

neuroscience↗