Publications by authors named "Mark S Lechner"
The ChlR1 DNA helicase, encoded by DDX11 gene, which is responsible for Warsaw breakage syndrome (WABS), has a role in sister-chromatid cohesion. In this study, we show that human ChlR1 deficient cells exhibit abnormal heterochromatin organization. While constitutive heterochromatin is discretely localized at perinuclear and perinucleolar regions in control HeLa cells, ChlR1-depleted cells showed dispersed localization of constitutive heterochromatin accompanied by disrupted centromere clustering.
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- - Cornelia de Lange Syndrome (CdLS) is a birth defect disorder often caused by mutations in the NIPBL gene, affecting chromosome cohesion and gene expression.
- - In a study with mice carrying a mutation in the Nipbl gene, researchers observed several CdLS-related defects, including growth delays, facial abnormalities, and high early mortality rates.
- - The research indicates that even a slight decrease in NIPBL levels (around 30%) leads to significant gene expression changes, particularly affecting genes related to body fat and potentially contributing to the symptoms of CdLS.
Sister-chromatid cohesion, the machinery used in eukaryote organisms to prevent aneuploidy, tethers sister chromatids together after their replication in S phase until mitosis. Previous studies in fission yeast, Drosophila and mammals have demonstrated the requirement for the heterochromatin formation pathway for proper centromeric cohesion. However, the exact role of heterochromatin protein 1 (HP1) in sister-chromatid cohesion in mammals is still unknown.
View Article and Find Full Text PDFThe HP1 proteins regulate epigenetic gene silencing by promoting and maintaining chromatin condensation. The HP1 chromodomain binds to methylated histone H3. More enigmatic is the chromoshadow domain (CSD), which mediates dimerization, transcription repression, and interaction with multiple nuclear proteins.
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- HP1 is crucial for gene silencing in Drosophila and, in mammalian cells, is linked to euchromatic regions and targeted by specific complexes for gene regulation.
- Researchers created a method to control HP1's binding to a transgene using a hormone-regulated system, leading to the transgene becoming tightly packed and silenced when the hormone is present.
- Notably, the silenced state remains stable for over 50 cell divisions even after the hormone is removed, indicating that HP1 can contribute to long-lasting epigenetic changes similar to those seen in fruit flies.
The Pax gene family encodes DNA-binding proteins that can both activate and repress transcription of specific target genes during embryonic development. Pax proteins are required for pattern formation and cell differentiation in a broad spectrum of developing tissues. Consistent with its expression in the intermediate mesoderm, the optic cup and stalk, and the otic vesicle, Pax2, a member of the Pax2/5/8 subfamily, is essential for the development of the renal epithelia, the optic cup, and the inner ear.
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