We have achieved mobilities in excess of 200,000 cm 2 V −1 s −1 at electron densities of ∼2×10 11 cm −2 by suspending single layer graphene. Suspension ∼150 nm above a Si/SiO2 gate electrode and electrical contacts to the graphene was achieved by a combination of electron beam lithography and etching. The specimens were cleaned in situ by employing current-induced heating, directly resulting in a significant improvement of electrical transport. Concomitant with large mobility enhancement, the widths of the characteristic Dirac peaks are reduced by a factor of 10 compared to traditional, non-suspended devices. This advance should allow for accessing the intrinsic transport properties of graphene. Graphene, the latest addition to the family of twodimensional (2D) materials, is distinguished from its cousins by its unusual band structure, rendering the quasiparticles in it formally identical to massless, chiral fermions. The experimental realization of graphene thus presents tantalizing opportunities to study phenomena ranging from the topological phase resulting in exotic quantum Hall states [1,2] to the famous Klein paradox -the anomalous tunneling of relativistic particles [3]. However, despite tremendous interest and concerted experimental efforts , the presence of strong impurity scattering -which limits the electron mean free path to less than a micron -has been a major barrier to progress. At the same time, there is strong evidence that graphene is a nearly perfect crystal free of the structural defects [4,5] that characterize most conductors. As a result, it has been put forth that the scattering of charge carriers stems from extrinsic sources [7,8,9,10].Although the exact nature of the scattering that limits the mobility of graphene devices remains unclear, evidence has mounted that interactions with the underlying substrate are largely responsible. Surface charge traps [6,7,8,9], interfacial phonons [11], substrate stabilized ripples [5,10,12], and fabrication residues on or under the graphene sheet may all contribute. Consequently, improving substrate quality or eliminating the substrate altogether by suspending graphene over a trench seems a promising strategy towards higher quality samples. While devices suspended over the substrate were achieved in the past [12,13], they lacked multiple electrical contacts thus precluding transport measurements.In this Letter we report the fabrication of electrically contacted suspended graphene and achieve a tenfold improvement in mobility as compared to the best values reported in the literature for traditional devices fabricated on a substrate. Besides opening new avenues for studying the intrinsic physics of Dirac fermions, this improvement demonstrates the dominant role played by extrinsic scattering in limiting the transport properties of unsuspended graphene samples.The fabrication of a suspended graphene device starts with optically locating a single-layer mechanically exfoliated graphene flake on top of a silicon substrate covered with 300 nm of SiO 2 . Singl...

Summary Topologically Associating Domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet mechanisms of TAD formation remain unclear. Here we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops, but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and other fine features of Hi-C data. Contrary to typical illustrations, each TAD consists of multiple loops dynamically formed through extrusion, rather than a single static loop. Loop extrusion both explains diverse experimental observations, including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments, and makes specific predictions for depletion of CTCF versus cohesin. Finally, loop extrusion has additional, potentially far-ranging, consequences for processes including enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.

Extracting biologically meaningful information from chromosomal interactions obtained with genome-wide chromosome conformation capture (3C) analyses requires elimination of systematic biases. We present a pipeline that integrates a strategy for mapping of sequencing reads and a data-driven method for iterative correction of biases, yielding genome-wide maps of relative contact probabilities. We validate ICE (Iterative Correction and Eigenvector decomposition) on published Hi-C data, and demonstrate that eigenvector decomposition of the obtained maps provides insights into local chromatin states, global patterns of chromosomal interactions, and the conserved organization of human and mouse chromosomes.

Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-large active and inactive compartments, and partitioning into sub-megabase domains (TADs). Yet, it remains unclear how these layers of organization form, interact with one another and impact genome functions. Here, we show that deletion of the cohesin-loading factor Nipbl, in mouse liver, leads to a dramatic reorganization of chromosomal folding. TADs and associated peaks vanish globally, even in the absence of transcriptional changes. In contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the 3D organization of the genome results from the interplay of two independent mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; 2) cohesin-dependent formation of TADs, possibly by loop extrusion, which contributes to guide distant enhancers to their target genes.