Project description:It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of CNVs within and between populations. However, CNV study of Chinese populations has been underrepresented considering the same efforts in other populations. Here we constructed a Chinese CNV map by using Affymetrix SNP 6 array. We did population analysis with other HapMap populations and identified population specific CNVs as well as candidate CNV regions under selection. Our results serve as a useful resource in further evolutionary and medical studies.
Project description:It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of CNVs within and between populations. However, CNV study of Chinese populations has been underrepresented considering the same efforts in other populations. Here we constructed a Chinese CNV map by using Affymetrix SNP 6 array. We did population analysis with other HapMap populations and identified population specific CNVs as well as candidate CNV regions under selection. Our results serve as a useful resource in further evolutionary and medical studies. There are 155 samples included in the analysis
Project description:Metazoans employ chromodomain helicase DNA-binding (CHD) enzymes to reposition nucleosomal DNA for transcription and replication. The CHD family consists of nine distinct members (CHD1-9) that possess highly conserved chromo and ATPase domains. These domains are flanked by poorly characterised N- and C-termini, which are enriched with intrinsically disordered regions (IDRs) and short aggregation-prone regions (APRs). The contribution of IDRs and APRs to CHD function has remained elusive. In this study we used affinity purification followed by mass spectrometry analysis (AP-MS) to define the protein-protein interaction (PPI) networks within the N- and C-termini of each CHD family member. The results illustrate a comprehensive map of CHD1-9-specific binding proteins that include dozens of novel interactions with transcription regulators and epigenetic factors. Using AlphaFold Multimer we examined the structural predictions of high confidence PPIs from our AP-MS screens and identified APR regions with alpha helical structures that contribute to PPIs. We further investigated a highly conserved APR within the C-terminus of the CHD4 protein and demonstrate that it contributes to the interaction of CHD4 with the nucleosome remodelling and deacetylase (NuRD) and CHD, ADNP, HP1 (ChAHP) complexes. Peptides mimicking this APR effectively disrupt CHD4 binding to both NuRD and ChAHP complexes, consequently triggering the transcriptional activation or repression of hundreds of target genes. Our results emphasise the crucial role that the N- and C-termini of CHD chromatin remodelers play in establishing protein-protein interaction (PPI) networks, which drive unique transcriptional programs.