Suman Mohajan
Education:
BS, Biochemistry and Molecular Biology, University of Chittagong, Bangladesh, 2007
MS, Biochemistry and Molecular Biology, University of Chittagong, Bangladesh, 2009
Dynamic alternation of three-dimensional (3D) architecture of chromatin and their spatial repositioning regulate many nuclear processes such as replication, DNA repair, gene expression, mRNA export etc. However, the underlying mechanism of chromatin architectural alteration has remained unexplored. Recently, our lab has uncovered a remarkable phenomenon of dynamic alternation of Heat Shock Protein (HSP) genes conformation upon their transcriptional activation, that is regulated by the heat shock transcription factor 1(Hsf1), in response to heat stress. Moreover, our lab and others have also observed that upon heat stress heat shock protein genes can reposition to the nuclear periphery. Studies from Jason H Brickner lab (JCB 2016) reported that inducible genes reposition and engage in inter-chromosomal clustering at the nuclear periphery and this is mediated by the interaction between transcription factors and nuclear pore complex protein(s). Furthermore, a previous study by Schneider et al. Cell (2015) showed that the nuclear pore-associated TREX2 complex can regulate gene expression by repositioning Mediator to nuclear pore complex. Therefore, my present research is focused on unveiling the answers to questions such as: does the coalescence phenomenon that we observe for HSP genes require nuclear repositioning of the genes to the NPC or is this phenomenon uncoupled with nuclear pore complex re-localization? Which factors are involved in this process? Unpublished observations of our lab suggest that Mediator might be involved in the coalescence of HSP gene upon heat shock. Does the interaction between Mediator and nuclear pore complex proteins actively participate in the HSP gene coalescence in response to heat shock?
Model: Nuclear basket proteins contribute to the 3D restructuring of HSR genes following the formation of HSR condensates.
Depicted is a model of events occurring in the nucleus of a budding yeast cell exposed to acute thermal stress.
- Heat shock induces the activation and binding of HSF1 to heat shock response elements located upstream of HSR genes (HSF1 clustering). Recruitment of HSF1 and Mediator may occur as a concerted event. Some clusters may exist as clouds over the HSR genes. Formation of these clusters is likely driven by both liquid-liquid phase separation (LLPS) and Interactions with spatially Clustered Binding Sites (ICBS) mechanisms.
- HSF1 then recruits components of the transcriptional machinery, leading to the formation of HSR condensates, again by both LLPS and ICBS mechanisms. These HSR condensates serve as the precursors for initiating transcription and the 3D reorganization of HSR genes.
- Roughly concurrent with the formation of HSR condensates and activation of HSR genes, nuclear basket proteins and other regulatory factors are recruited to these genes. These factors then drive the physical clustering of HSR genes that occurs predominantly within the nucleoplasm.
- Subsequently, the HSR chromatin clusters reposition to the NPC for post-transcriptional events such as mRNA multiplexing. Such repositioning and multiplexing may enhance the processing, export, and/or preferential translation of HSR mRNAs.
Ref.: Mohajan, S., Rubio, L.S. and Gross, D.S. 2025. Nuclear basket proteins Nup2 and Mlp1 drive heat shock-induced 3D genome restructuring downstream of transcriptional activation. J. Biol. Chem. 301:110568.
