Browsing by Author "Zhang, Jie"

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Open Access
Chromatin-associated APC regulates gene expression in collaboration with canonical WNT signaling and AP-1.
(Oncotarget, 2018-07-27) Hankey, William; Chen, Zhong; Bergman, Maxwell J; Fernandez, Max O; Hancioglu, Baris; Lan, Xun; Jegga, Anil G; Zhang, Jie; Jin, Victor X; Aronow, Bruce J; Wang, Qianben; Groden, Joanna
Mutation of the APC gene occurs in a high percentage of colorectal tumors and is a central event driving tumor initiation in the large intestine. The APC protein performs multiple tumor suppressor functions including negative regulation of the canonical WNT signaling pathway by both cytoplasmic and nuclear mechanisms. Published reports that APC interacts with β-catenin in the chromatin fraction to repress WNT-activated targets have raised the possibility that chromatin-associated APC participates more broadly in mechanisms of transcriptional control. This screening study has used chromatin immunoprecipitation and next-generation sequencing to identify APC-associated genomic regions in colon cancer cell lines. Initial target selection was performed by comparison and statistical analysis of 3,985 genomic regions associated with the APC protein to whole transcriptome sequencing data from APC-deficient and APC-wild-type colon cancer cells, and two types of murine colon adenomas characterized by activated Wnt signaling. 289 transcripts altered in expression following APC loss in human cells were linked to APC-associated genomic regions. High-confidence targets additionally validated in mouse adenomas included 16 increased and 9 decreased in expression following APC loss, indicating that chromatin-associated APC may antagonize canonical WNT signaling at both WNT-activated and WNT-repressed targets. Motif analysis and comparison to ChIP-seq datasets for other transcription factors identified a prevalence of binding sites for the TCF7L2 and AP-1 transcription factors in APC-associated genomic regions. Our results indicate that canonical WNT signaling can collaborate with or antagonize the AP-1 transcription factor to fine-tune the expression of shared target genes in the colorectal epithelium. Future therapeutic strategies for APC-deficient colorectal cancers might be expanded to include agents targeting the AP-1 pathway.
Open Access
Shear-induced rigidity of frictional particles: Analysis of emergent order in stress space.
(Phys Rev E, 2016-04) Sarkar, Sumantra; Bi, Dapeng; Zhang, Jie; Ren, Jie; Behringer, RP; Chakraborty, Bulbul
Solids are distinguished from fluids by their ability to resist shear. In equilibrium systems, the resistance to shear is associated with the emergence of broken translational symmetry as exhibited by a nonuniform density pattern that is persistent, which in turn results from minimizing the free energy. In this work, we focus on a class of systems where this paradigm is challenged. We show that shear-driven jamming in dry granular materials is a collective process controlled by the constraints of mechanical equilibrium. We argue that these constraints can lead to a persistent pattern in a dual space that encodes the statistics of contact forces and the topology of the contact network. The shear-jamming transition is marked by the appearance of this persistent pattern. We investigate the structure and behavior of patterns both in real space and the dual space as the system evolves through the rigidity transition for a range of packing fractions and in two different shear protocols. We show that, in the protocol that creates homogeneous jammed states without shear bands, measures of shear jamming do not depend on strain and packing fraction independently but obey a scaling form with a packing-fraction-dependent characteristic strain that goes to zero at the isotropic jamming point ϕ_{J}. We demonstrate that it is possible to define a protocol-independent order parameter in this dual space, which provides a quantitative measure of the rigidity of shear-jammed states.
Open Access
Transition dynamics and magic-number-like behavior of frictional granular clusters.
(Phys Rev E Stat Nonlin Soft Matter Phys, 2012-07) Tordesillas, Antoinette; Walker, David M; Froyland, Gary; Zhang, Jie; Behringer, Robert P
Force chains, the primary load-bearing structures in dense granular materials, rearrange in response to applied stresses and strains. These self-organized grain columns rely on contacts from weakly stressed grains for lateral support to maintain and find new stable states. However, the dynamics associated with the regulation of the topology of contacts and strong versus weak forces through such contacts remains unclear. This study of local self-organization of frictional particles in a deforming dense granular material exploits a transition matrix to quantify preferred conformations and the most likely conformational transitions. It reveals that favored cluster conformations reside in distinct stability states, reminiscent of "magic numbers" for molecular clusters. To support axial loads, force chains typically reside in more stable states of the stability landscape, preferring stabilizing trusslike, three-cycle contact triangular topologies with neighboring grains. The most likely conformational transitions during force chain failure by buckling correspond to rearrangements among, or loss of, contacts which break the three-cycle topology.