Biophysics of Chromatin Remodeling

Abstract

As primary carriers of epigenetic information and gatekeepers of genomic DNA, nucleosomes are essential for proper growth and development of all eukaryotic cells. Although they are intrinsically dynamic, nucleosomes are actively reorganized by ATP-dependent chromatin remodelers. Chromatin remodelers contain helicase-like ATPase motor domains that can translocate along DNA, and a long-standing question in the field is how this activity is used to reposition or slide nucleosomes. In addition to ratcheting along DNA like their helicase ancestors, remodeler ATPases appear to dictate specific alternating geometries of the DNA duplex, providing an unexpected means for moving DNA past the histone core. Emerging evidence supports twist-based mechanisms for ATP-driven repositioning of nucleosomes along DNA. In this review, we discuss core experimental findings and ideas that have shaped the view of how nucleosome sliding may be achieved. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

H2A.Z deposition by SWR1C involves multiple ATP-dependent steps

“…However, unlike other remodelers that mobilize nucleosomes, only 2nt ssDNA gaps within the ATPase binding site at SHL2 block dimer exchange (±17bp to ±22bp from the nucleosomal dyad) (Ranjan et al, 2015), suggesting that the Swr1 ATPase lobes may translocate only 1-2bp of DNA. Alternatively, the gaps near SHL±2 may block SWR1C-induced deformations in DNA that precede a putative translocation step (Nodelman and Bowman, 2021). Our previous ensemble FRET studies were unable to detect translocation of DNA at the nucleosomal edge (Singh et al, 2019), and our histone-DNA crosslinking analyses presented here were also unable to detect changes in the path of nucleosomal DNA between the DNA entry point and SHL2.…”

Nucleosome-induced homology recognition in chromatin

“…But, again, the distribution of nucleosomes, even on identical sequences, may not necessarily be identical. Moving a nucleosome out of its preferential position may require 20-30 k B T of energy [28] and the action of molecular motors-chromatin remodellers [27]. Thus, the assumption of similar nucleosome-related charge distributions for homologous DNAs may be a reasonable approximation for a large fraction of chromatin.…”

“…To investigate the effect of structural homology of nucleosome arrays on the processes mentioned above, one has to consider the partial or full unfolding of the nucleosome that allows the juxtaposition of naked DNA sequences. Temporary nucleosome unwrapping and repositioning does indeed happen in vivo, facilitated by thermal fluctuations [26] and active energy-dependent chromatin remodelling [27]. However, histones bind tightly to DNA with an energy of the order of approximately 20-30 k B T [28], and so it is energetically costly to fully remove them from these regions.…”

Nucleosome induced homology recognition in chromatin

“…But again, the distribution of nucleosomes, even on identical sequences, may not necessarily be identical. Moving a nucleosome out of its preferential position may require 20-30 kBT of energy 28 and the action of molecular motors -chromatin remodellers 27 . Thus, the assumption of similar nucleosome-related charge distributions for homologous DNAs may be a reasonable approximation for a large fraction of chromatin.…”

“…To investigate the effect of structural homology of nucleosome arrays on the processes mentioned above, one has to consider partial or full unfolding of the nucleosome that allows the juxtaposition of naked DNA sequences. Temporary nucleosome unwrapping and repositioning does indeed happen in vivo, facilitated by thermal fluctuations 26 and active energy-dependent chromatin remodelling 27 . However, histones bind tightly to DNA with an energy on the order of ~20-30 kBT 28 , and so it is energetically costly to fully remove them from these regions.…”