Biology subjects

Parsania, C.

Publications and source records attributed to Parsania, C..

3 recordsLinked to original sources

bioRxiv2025

The ZNF512B-NuRD complex co-ordinates a neural-specific gene expression program

The nucleosome remodelling and deacetylase complex (NuRD) plays a key role in chromatin regulation and a wide range of biological processes including development, haemopoiesis, immunity and neurogenesis. Its interaction with tissue-enriched and sequence-specific transcription factors (TFs) leads to distinct functional outputs in the given tissue by targeting a specific set of genes. However, how NuRD dynamically and specifically regulates gene expression in a tissue-specific manner is poorly understood. Here, we refine an N-terminal specific NuRD interaction motif which enables direct engagement with many transcriptional regulatory proteins. Using a series of structural modelling and biochemical techniques, we show that ZNF512B, a poorly characterised neuronal-expressed zinc finger protein, directly binds to the RBBP4 subunit of the NuRD complex. Subsequent knockdown of ZNF512B results in the downregulation of several neural-related molecular pathways suggesting that ZNF512B may play a regulatory role during neurogenesis. We also show that in NTERA-2 neural cells, the expression of ZNF512B is necessary for cell growth and survival, and is markedly enhanced during neural progenitor cell (NPC) differentiation. In summary, our data suggest that ZNF512B might regulate neural-specific transcriptional programs via engagement with the NuRD complex.

molecular biology↗

bioRxiv2024

Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers

Chromodomain helicase DNA-binding (CHD1-9) enzymes reposition nucleosomal DNA for transcription, recombination, and replication. They possess highly conserved ATPase domains flanked by poorly characterised N- and C-termini, which are enriched with intrinsically disordered regions (IDRs) and short aggregation-prone regions (APRs). The roles of IDRs and APRs in CHD function has remained elusive. Here, by integrating proteomics and AlphaFold Multimer analysis, we defined the protein-protein interaction (PPI) networks within the N- and C-termini of all CHDs. We generated a comprehensive map of CHD1-9-specific binding proteins, revealing dozens of novel interactions with transcription regulators. We identified APR regions that contribute to PPI formation and demonstrated that a highly conserved APR within the C-terminus of CHD4 is critical for its interaction with the nucleosome remodeling and deacetylase (NuRD), as well as the CHD, ADNP, and HP1 (ChAHP) complexes. Further analysis unravels a regulatory role for the CHD4 APR in gene transcription during erythrocyte formation. Our results emphasize that the N- and C-termini of CHD chromatin remodelers establish PPI networks that drive unique transcriptional programs.

biochemistry↗

bioRxiv2021

Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and drug resistance

Candida glabrata can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How C. glabrata reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in C. glabrata to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic C. glabrata responses to macrophage with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects azole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for C. glabratas survival in macrophages and drug tolerance.

microbiology↗