please proof read for me.   HSPs Regulatory Cascades
HSPs account for 5-10% of the total cellular protein content under normal physiological conditions. However, in response to various cellular or environmental stress cues, the heat shock transcription factors (HSFs) are activated, leading a dramatic upregulation of HSPs expression (up to 2 to 3 times increase in cellular concentration) in order to neutralize the stresses. 
In fact, HSP regulatory cascades is a tightly coordinated at both transcriptional and post-transcriptional levels. Here, HSP70 will be used an example as it is one of the main and robust transcriptional inducible genes among all HSPs families. Figure 2. illustrates the HSP regulatory cascades occurs within cells under both unstressed (Figure 2a.) and stressed condition (Figure 2b). Under unstressed/ normal physiological conditions, the loci of HSP70 genes are neither present in a compact hetero-chromatin domain nor marked by repressive epigenetics histone modification. The promoter and 3’ end of HSP70 gene is nucleosome-free while its gene body is covered by nucleosomes. 
The structure of Hsp70 gene promoter is illustrated in Figure 3. At the promoter region, it contains one or more binding sites, known as heat shock elements (HSEs).  And, HSE comprises of more than three nGAAn repeats, organised from head to tail in the promoter region. Moreover, besides equipped with HSE, the hsp70 promoter is also bound by a paused RNA polymerase II (Pol II). These features ensure the rapid transcriptional activation of HSP70 in response to the binding of Heat shock factor 1 (HSF1). 
Meanwhile, HSF1 acts as the master transcription factor of Hsp70 gene. It contains three domains: (i) an oligomerization domain next to the DNA binding domain at the N-terminus, (ii) a regulatory domain in the middle that negatively regulates the function of the trans-activation domain in unstressed conditions and (iii) a trans-activation domain at the C-terminus that induces transcription initiation and elongation (Figure 2c). Under normal circumstance, HSF1 is kept as an inactive monomer by its constitutive members; HSP90 and HSP70 families. It shuttles between the nucleus and cytoplasm (Figure 2a). 
However, cellular or environmental stress cues cause the accumulation of proteotoxic misfolded and aggregated proteins, and result in the rapid activation of HSF1. HSF1 is released from HSPs, trimerizes and subsequently translocate into the nucleus. Co-activators, such as P-TEFb, Spt6, and Topo I are recruited simultaneously and ultimately leads to an increase in the Hsp70 mRNA transactivation and protein translation. The elevation of cytosolic HSP levels promote the refolding of misfolded proteins (Figure 2b). As the cellular proteostasis is achieved, a negative feedback loop mechanism is established. HSPs will stop the continuous HSF1 activity. 
Figure 3. illustrates the process of HSF1 trimerization and binds to the Hsp promoter. During HSF-1 trimerization, each HSF1 in the trimer binds to an nGAAn repeat via its DNA binding domain. This process enhances the binding affinity of HSF1 to HSE in the Hsp70 promoter. Nonetheless, the binding of HSF1 to HSE is insufficient to activate HSPs transcription. HSF1 needs to undergo extensive series of post-translational modifications. For examples, hyperphosphorylation of serine and threonine residues on the regulatory domain; the removal of sumo groups (possess an transcription inhibitory effect) and acetylation at different lysine residues of HSF1.