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Acetylation of lysine residues is an important and common post-translational regulatory mechanism occurring on thousands of non-histone proteins. Lysine deacetylases (KDACs or HDACs) are a family of enzymes responsible for removing acetylation. To identify the biological mechanisms regulated by individual KDACs, we created HT1080 cell lines containing chromosomal point mutations, which endogenously express either KDAC6 or KDAC8 having single inactivated catalytic domain. Engineered HT1080 cells expressing inactive KDA6 or KDAC8 domains remained viable and exhibited enhanced acetylation on known substrate proteins. RNA-seq analysis revealed that many changes in gene expression were observed when KDACs were inactivated, and that these gene sets differed significantly from knockdown and knockout cell lines. Using GO ontology, we identified several critical biological processes associated specifically with catalytic activity and others attributable to non-catalytic interactions. Treatment of wild-type cells with KDAC-specific inhibitors Tubastatin A and PCI-34051 resulted in gene expression changes distinct from those of the engineered cell lines, validating this approach as a tool for evaluating in-cell inhibitor specificity and identifying off-target effects of KDAC inhibitors. Probing the functions of specific KDAC domains using these cell lines is not equivalent to doing so using previously existing methods and provides novel insight into the catalytic functions of individual KDACs by investigating the molecular and cellular changes upon genetic inactivation.

 

We investigate the occurrence of repeating glacial seismicity near the grounding line of the Foundation Ice Stream and further upstream using continuous broadband seismic data collected by Polar Earth Observing Network (POLENET/A‐NET) stations from 2014 through 2019. Through manual identification and cross‐correlation analysis, 2,237 discrete icequakes (1.5  M_L  2.6) are detected in two spatial clusters, one located at the grounding line of the Foundation Ice Stream (2,219 event detections) and a second located further upstream proximal to a subglacial ridge (18 event detections). Seismicity is predominantly concentrated in the Schmidt Hills, located adjacent to the grounding line of the Foundation Ice Stream, and shows clear ocean tide modulation. Seismic events primarily occur during spring tides, and, on a shorter timescale, concurrent with the rising tide preceding daily maximum high tide. The seismicity can be attributed to stick‐slip motion and fracturing that preferentially occur during rising tides. Seismicity located further upstream in the southern portion of the Foundation Ice Stream most likely reflects basal stick‐slip processes associated with the subglacial topographic high.

 

Abstract The Transantarctic Mountains (TAMs), Antarctica, exhibit anomalous uplift and volcanism and have been associated with regions of thermally perturbed upper mantle that may or may not be connected to lower mantle processes. To determine if the anomalous upper mantle beneath the TAMs connects to the lower mantle, we interrogate the mantle transition zone (MTZ) structure under the TAMs and adjacent parts of East Antarctica using 12,500+ detections of P-to-S conversions from the 410 and 660 km discontinuities. Our results show distinct zones of thinner-than-global-average MTZ (∼205–225 km, ∼10%–18% thinner) beneath the central TAMs and southern Victoria Land, revealing throughgoing convective thermal anomalies (i.e., mantle plumes) that connect prominent upper and lower mantle low-velocity regions. This suggests that the thermally perturbed upper mantle beneath the TAMs and Ross Island may have a lower mantle origin, which could influence patterns of volcanism and TAMs uplift.