Ashok Kumar Patel

Bio: Ashok Kumar Patel is an academic researcher from Indian Institute of Technology Delhi. The author has contributed to research in topics: Nucleosome & Chromatin. The author has an hindex of 18, co-authored 52 publications receiving 801 citations. Previous affiliations of Ashok Kumar Patel include University of Oulu & Indian Institutes of Technology.

Dynamic regulation of transcription factors by nucleosome remodeling

Abstract: The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

Chromatin remodelers: We are the drivers!!

Abstract: Chromatin is a highly dynamic structure that imparts structural organization to the genome and regulates the gene expression underneath. The decade long research in deciphering the significance of epigenetics in maintaining cellular integrity has embarked the focus on chromatin remodeling enzymes. These drivers have been categorized as readers, writers and erasers with each having significance of their own. Largely, on the basis of structure, ATP dependent chromatin remodelers have been grouped into 4 families; SWI/SNF, ISWI, IN080 and CHD. It is still unclear to what degree these enzymes are swayed by local DNA sequences when shifting a nucleosome to different positions. The ability of regulating active and repressive transcriptional state via open and close chromatin architecture has been well studied however, the significance of chromatin remodelers in regulating transcription at each step i.e. initiation, elongation and termination require further attention. The authors have highlighted the significance and role of different chromatin remodelers in transcription, DNA repair and histone variant deposition.

ATP-dependent chromatin assembly is functionally distinct from chromatin remodeling.

Abstract: Chromatin assembly involves the combined action of ATP-dependent motor proteins and histone chaperones. Because motor proteins in chromatin assembly also function as chromatin remodeling factors, we investigated the relationship between ATP-driven chromatin assembly and chromatin remodeling in the generation of periodic nucleosome arrays. We found that chromatin remodeling-defective Chd1 motor proteins are able to catalyze ATP-dependent chromatin assembly. The resulting nucleosomes are not, however, spaced in periodic arrays. Wild-type Chd1, but not chromatin remodeling-defective Chd1, can catalyze the conversion of randomly-distributed nucleosomes into periodic arrays. These results reveal a functional distinction between ATP-dependent nucleosome assembly and chromatin remodeling, and suggest a model for chromatin assembly in which randomly-distributed nucleosomes are formed by the nucleosome assembly function of Chd1, and then regularly-spaced nucleosome arrays are generated by the chromatin remodeling activity of Chd1. These findings uncover an unforeseen level of specificity in the role of motor proteins in chromatin assembly. DOI:http://dx.doi.org/10.7554/eLife.00863.001.

Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes

Abstract: Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation. We propose the 'hourglass' model of remodeller function, in which each remodeller subfamily utilizes diverse specialized proteins and protein domains to assist in nucleosome targeting or to differentially detect nucleosome epitopes. These modules converge to regulate a common DNA translocation mechanism, to inform the conserved ATPase 'motor' on whether and how to apply DNA translocation, which together achieve the various outcomes of chromatin remodelling: nucleosome assembly, chromatin access and nucleosome editing.

Post-translational modifications of histones that influence nucleosome dynamics.

Abstract: Nucleosomes are efficient DNA-packaging units. The fundamental protein unit of the nucleosome is the histone dimer, a simple α-helical domain possessing a highly basic, curved surface that closely matches the phosphate backbone of bent duplex DNA. Two copies each of histone heterodimer, H3/H4 and H2A/H2B, form a histone octamer that is wrapped with approximately 146 bp of duplex DNA in a left-handed spiral1,2 (Figure ​(Figure1).1). Through extensive electrostatic and hydrogen-bonding interactions, each histone dimer coordinates three consecutive minor grooves on the inner surface of the DNA spiral. The bending of DNA over the protein surface brings the phosphate backbone of the two strands closer together on the inside of the spiral, narrowing the major and minor grooves of DNA, while widening the grooves on the outside. This bent conformation of the DNA duplex, which would otherwise be energetically unfavorable, is maintained through charge neutralization from numerous arginine and lysine side chains of the histones. Open in a separate window Figure 1 Overview of nucleosome architecture. (A) Illustration of H2A/H2B and H3/H4 heterodimers and how they fit together to form the histone octamer. (B) Face and top view of the nucleosome structure. For this and all subsequent molecular representations of the nucleosome, the high-resolution crystal structure (PDB code 1KX5) was used.93