A5080185154- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Animal Genetics and Reproduction
- Autism Spectrum Disorder Research
- Histone Deacetylase Inhibitors Research
- Nuclear Receptors and Signaling
- Signaling Pathways in Disease
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
University of Michigan
2012-2023
Michigan Medicine
2019-2023
ID Genomics (United States)
2019
Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated X-linked intellectual disability (XLID) patients. Here, we report that disruption the mouse Kdm5c gene recapitulates adaptive cognitive abnormalities observed XLID, including impaired social behavior, memory deficits, aggression. Kdm5c-knockout brains exhibit abnormal dendritic arborization, spine...
Intellectual disability (ID) affects up to 2% of the population world-wide and often coincides with other neurological conditions such as autism spectrum disorders. Mutations in KDM5C cause Mental Retardation, X-linked, Syndromic, Claes-Jensen type (MRXSCJ, OMIM #300534) are one most common causes X-linked ID. encodes a histone demethylase for di- tri-methylated H3 lysine 4 (H3K4me2/3), chromatin marks which enriched transcriptionally-engaged promoter regions. regulates gene transcription;...
Abstract XX female and XY male therian mammals equalize X-linked gene expression through the mitotically-stable transcriptional inactivation of one two X chromosomes in somatic cells. Here, we describe an essential function homolog ancestral X-Y pair, Kdm5c - Kdm5d , Xist lncRNA, which is required for stable X-inactivation. Ablation females results a significant reduction RNA expression. encodes demethylase that enhances by converting histone H3K4me2/3 modifications into H3K4me1. Ectopic...
Abstract Histone H3 lysine 4 methylation (H3K4me) is extensively regulated by numerous writer and eraser enzymes in mammals. Nine H3K4me are associated with neurodevelopmental disorders to date, indicating their important roles the brain. However, interplay among during brain development remains largely unknown. Here, we show functional interactions of a writer-eraser duo, KMT2A KDM5C , which responsible for Wiedemann-Steiner Syndrome (WDSTS), mental retardation X-linked syndromic...
Chromatin dysregulation has emerged as a major hallmark of neurodevelopmental disorders such intellectual disability (ID) and autism spectrum (ASD). The prevalence ID ASD is higher in males compared to females, with unknown mechanisms. Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MRXSCJ), caused by loss-of-function mutations lysine demethylase 5C (
Abstract Histone H3 lysine 4 methylation (H3K4me) is extensively regulated by numerous writer and eraser enzymes in mammals. Nine H3K4me are associated with neurodevelopmental disorders to date, indicating their important roles the brain. However, interplay among during brain development remains largely unknown. Here, we show functional interactions of a writer-eraser duo, KMT2A KDM5C , which responsible for Wiedemann-Steiner Syndrome (WDSTS), mental retardation X-linked syndromic...
SUMMARY XY male and XX female mammals equalize X-linked gene expression through the mitotically-stable transcriptional inactivation of an X-chromosome in females. Although most genes are silent on inactive-X, some escape silencing expressed at higher levels females vs. males. Here, we show that escapee Smcx / Kdm5c , encoding a histone H3K4me2/3 demethylase, underlies female-specific induction X-inactivation. Mouse embryonic epiblast cells differentiating stem (ESCs) lacking SMCX reduced...
An amendment to this paper has been published and can be accessed via a link at the top of paper.