Large-scale Conformation Research Articles

The evolution of low-mass central galaxies in the vicinity of massive structures and its impact on the two-halo conformity

We investigated the population of low-mass central galaxies with M$_ star $ $h^ $ M$_ odot $, inhabiting regions near massive groups and clusters of galaxies using the IllustrisTNG300 and MDPL2-SAG simulations. We set out to study their evolutionary histories, aiming to find hints about the large-scale conformity signal they produce. We also used a control sample of central galaxies with the same stellar mass range located far away from massive structures. For both samples, we find a subpopulation of galaxies accreted by another halo in the past, but now considered central galaxies; we refer to these objects as former satellites. The number of former satellites is higher for quenched central galaxies near massive systems, with fractions of 45<!PCT!> and 17<!PCT!> in IllustrisTNG300 and MDPL2-SAG, respectively. The differences in the numerical resolution of each simulation lead to the different fractions of former satellites. Our results in TNG300 show that former satellites ``pollute'' the sample of central galaxies because they suffered environmental processes when they were satellites hosted typically by massive dark matter halos (M$_ $ $h^ $ M$_ odot $) since $z 0.5$. After removing former satellites, the evolutionary trends for quenched central galaxies near massive structures are fairly similar to those of the quenched control galaxies, showing small differences at low redshift. For MDPL2-SAG instead, former satellites were hosted by less massive halos, with a mean halo mass around $ $h^ $ M$_ odot $, and the evolutionary trends remain equal before and after removing former satellite galaxies. We also measured the two-halo conformity, that is, the correlation in the specific star formation rate between low-mass central galaxies and their neighbors at megaparsec scales, and how former satellites contribute to the signal at three different redshifts: $z=0, 0.3,$ and 1. The time evolution of the conformity signal in the simulations presents apparent contradictory results: it decreases from $z=0$ to $z=1$ in MDPL2-SAG, while it increases in TNG300. However, after removing former satellites in the latter, the signal is strongly reduced, but practically does not change at $z 0.3$, and it disappears at $z=1$. We compare our findings with recent literature data and discuss the conformity measurements, as different approaches can lead to varying results.

A fine-scale Arabidopsis chromatin landscape reveals chromatin conformation-associated transcriptional dynamics

Plants, as sessile organisms, deploy transcriptional dynamics for adapting to extreme growth conditions such as cold stress. Emerging evidence suggests that chromatin architecture contributes to transcriptional regulation. However, the relationship between chromatin architectural dynamics and transcriptional reprogramming in response to cold stress remains unclear. Here, we apply a chemical-crosslinking assisted proximity capture (CAP-C) method to elucidate the fine-scale chromatin landscape, revealing chromatin interactions within gene bodies closely associated with RNA polymerase II (Pol II) densities across initiation, pausing, and termination sites. We observe dynamic changes in chromatin interactions alongside Pol II activity alterations during cold stress, suggesting local chromatin dynamics may regulate Pol II activity. Notably, cold stress does not affect large-scale chromatin conformations. We further identify a comprehensive promoter-promoter interaction (PPI) network across the genome, potentially facilitating co-regulation of gene expression in response to cold stress. Our study deepens the understanding of chromatin conformation-associated gene regulation in plant response to cold.

Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity

Cell fate transitions observed in embryonic development involve changes in three-dimensional genomic organization that provide proper lineage specification. Whether similar events occur within tumor cells and contribute to cancer evolution remains largely unexplored. We modeled this process in the pediatric cancer Ewing sarcoma and investigated high-resolution looping and large-scale nuclear conformation changes associated with the oncogenic fusion protein EWS-FLI1. We show that chromatin interactions in tumor cells are dominated by highly connected looping hubs centered on EWS-FLI1 binding sites, which directly control the activity of linked enhancers and promoters to establish oncogenic expression programs. Conversely, EWS-FLI1 depletion led to the disassembly of these looping networks and a widespread nuclear reorganization through the establishment of new looping patterns and large-scale compartment configuration matching those observed in mesenchymal stem cells, a candidate Ewing sarcoma progenitor. Our data demonstrate that major architectural features of nuclear organization in cancer cells can depend on single oncogenes and are readily reversed to reestablish latent differentiation programs.

Re-Balancing Replica Exchange with Solute Tempering for Sampling Dynamic Protein Conformations.

Replica exchange with solute tempering (REST) is a highly effective variant of replica exchange for enhanced sampling in explicit solvent simulations of biomolecules. By scaling the Hamiltonian for a selected "solute" region of the system, REST effectively applies tempering only to the degrees of freedom of interest but not the rest of the system ("solvent"), allowing fewer replicas for covering the same temperature range. A key consideration of REST is how the solute-solvent interactions are scaled together with the solute-solute interactions. Here, we critically evaluate the performance of the latest REST2 protocol for sampling large-scale conformation fluctuations of intrinsically disordered proteins (IDPs). The results show that REST2 promotes artificial protein conformational collapse at high effective temperatures, which seems to be a designed feature originally to promote the sampling of reversible folding of small proteins. The collapse is particularly severe with larger IDPs, leading to replica segregation in the effective temperature space and hindering effective sampling of large-scale conformational changes. We propose that the scaling of the solute-solvent interactions can be treated as free parameters in REST, which can be tuned to control the solute conformational properties (e.g., chain expansion) at different effective temperatures and achieve more effective sampling. To this end, we derive a new REST3 protocol, where the strengths of the solute-solvent van der Waals interactions are recalibrated to reproduce the levels of protein chain expansion at high effective temperatures. The efficiency of REST3 is examined using two IDPs with nontrivial local and long-range structural features, including the p53 N-terminal domain and the kinase inducible transactivation domain of transcription factor CREB. The results suggest that REST3 leads to a much more efficient temperature random walk and improved sampling efficiency, which also further reduces the number of replicas required. Nonetheless, our analysis also reveals significant challenges of relying on tempering alone for sampling large-scale conformational fluctuations of disordered proteins. It is likely that more efficient sampling protocols will require incorporating more sophisticated Hamiltonian replica exchange schemes in addition to tempering.

Unveiling Cas8 dynamics and regulation of a transposon-encoded cascade-TniQ complex.

Csy (CRISPR-System Yersinia, or ‘Cascade’) is a class 1, type 1F CRISPR-Cas system which utilizes RNA-guided strand invasion to target viral DNA and designate it for cleavage by an external nuclease (Cas2/3). It has been recently shown, in Vibrio Cholerae, that there exists a variant of Cascade encoded in a transposon (Tn6677). This variant binds to a TniQ homodimer, resulting in a ‘Cascade-TniQ’ complex which, unlike the original Cascade that targets viral DNA for cleavage, recruits a heteromeric transposase responsible for integration of Tn6677. This integration process starts with binding of Cascade's crRNA to the DNA target sequence located in the bacterial genome, resulting in the formation of the ‘R Loop,’ this step is the focus of the current research. Both classical molecular dynamics (cMD) and enhanced sampling methods (GaMD) have been employed to better understand the dynamical state of the system in the RNA-only and the DNA-bound configurations. We have found evidence for a multi-state like behavior, with drastic differences in the state population and transition barriers upon DNA binding. Furthermore, it appears that the TniQ homodimer undergoes changes in large-scale conformations dependent on its level of intrinsic stability. This allowed us to make a tentative claim on a role of Zinc-coordination within TniQ's Zinc-finger binding domains. Tying our findings together with data from literature allowed us to make general comments on how the RNA-bound state and R Loop formation may be regulated. Hopefully, these findings will eventually allow for a more streamlined effort in re-engineering Cascade-TniQ for use in mammalian cells.

Stabilization of membrane topologies by proteinaceous remorin scaffolds

In plants, the topological organization of membranes has mainly been attributed to the cell wall and the cytoskeleton. Additionally, few proteins, such as plant-specific remorins have been shown to function as protein and lipid organizers. Root nodule symbiosis requires continuous membrane re-arrangements, with bacteria being finally released from infection threads into membrane-confined symbiosomes. We found that mutations in the symbiosis-specific SYMREM1 gene result in highly disorganized perimicrobial membranes. AlphaFold modelling and biochemical analyses reveal that SYMREM1 oligomerizes into antiparallel dimers and may form a higher-order membrane scaffolding structure. This was experimentally confirmed when expressing this and other remorins in wall-less protoplasts is sufficient where they significantly alter and stabilize de novo membrane topologies ranging from membrane blebs to long membrane tubes with a central actin filament. Reciprocally, mechanically induced membrane indentations were equally stabilized by SYMREM1. Taken together we describe a plant-specific mechanism that allows the stabilization of large-scale membrane conformations independent of the cell wall.

The physical origin of galactic conformity: from theory to observation

ABSTRACT We employ several galaxy formation models, particularly, L-GALAXIES, IllustrisTNG, and EAGLE, as well as observational samples from SDSS and dark energy spectroscopic intstrument (DESI), to investigate galactic conformity, the observed correlation between the star-formation properties of central (primary) galaxies and those of their neighbours. To analyse the models and observations uniformly, we introduce CenSat, a new algorithm to define whether a galaxy is a central or a satellite system. We find that the conformity signal is present, up to at least 5 Mpc from the centres of low- and intermediate-mass centrals in the latest version of L-GALAXIES (Ayromlou et al. 2021b), IllustrisTNG, and EAGLE, as well as in SDSS and DESI observational samples. In comparison, the conformity signal is substantially weaker in an older version of L-GALAXIES (Henriques et al. 2020). One of the main differences between this older model and the other models is that except for satellites within the boundaries of massive cluster haloes, it neglects ram-pressure stripping of the gas reservoirs of galaxies (e.g. in groups and cluster outskirts). Our observational comparisons demonstrate that this difference significantly affects the observed large-scale conformity signal. Furthermore, by examining the contribution of backsplash, fly-by, central, and satellite galaxies to the conformity signal, we show that much, but not all, of it arises from primary galaxies near massive systems. Remaining tensions between the models and observations may be solved by modifying the physical prescriptions for how feedback processes affect the distribution and kinematics of gas and the environment around galaxies out to scales of several Megaparsecs.

Active Remodeling of Chromatin and Implications for In Vivo Folding.

Building on the observation that chromatin compaction can be locally modulated by activity, we propose a model of in vivo chromatin as an active polymer and study its large scale conformations. In particular, we study an active mechanochemical model of chromosomal folding based on the interplay among polymer elasticity, confinement, topological constraints, and fluctuating active stresses arising from the ATP-dependent action of a variety of chromatin-associated protein machines and chromatin-remodeling proteins and their stochastic turnover. We find that activity drives the chromatin to a nonequilibrium steady state; the statistics of conformations in this nonequilibrium steady state are consistent with recent measurements on intrachromosomal contact probabilities and chromosomal compaction. The contact exponents at steady state show a systematic variation with changes in the nature of activity and the rates of turnover. The steady state configuration of the active chromatin in two dimensions resembles a space-filling Peano curve, which might have implications for the optimization of genome information storage.

Substrate-dependent transport mechanism in AcrB of multidrug resistant bacteria.

The multidrug resistance (MDR) system effectively expels antibiotics out of bacteria causing serious issues during bacterial infection. In addition to drug, indole, a common metabolic waste of bacteria, is expelled by MDR system of gram-negative bacteria for their survival. Experimental results suggest that AcrB, one of the key components of MDR system, undergoes large scale conformation changes during the pumping due to proton-motive process. However, due to extremely short time scale, it is difficult to observe (experimentally) those changes in the AcrB, which might facilitate the pumping process. Molecular simulations can shed light to understand the conformational changes for transport of indole in AcrB. Examination of conformational changes using all-atom simulation is, however, impractical. Here, we develop a hybrid coarse-grained force field to study the conformational changes of AcrB in presence of indole in the porter domain of monomer II. Using the coarse-grained force field, we investigated the conformational changes of AcrB for a number of model systems considering the effect of protonation in aspartic acid (Asp) residues Asp407 and Asp408 in the transmembrane domain of monomer II. Our results show that in the presence of indole, protonation of Asp408 or Asp407 residue causes conformational changes from binding state to extrusion state in monomer II, while remaining two monomers (I and III) approach access state in AcrB protein. We also observed that all three AcrB monomers prefer to go back to access state in the absence of indole. Steered molecular dynamics simulations were performed to demonstrate the feasibility of indole transport mechanism for protonated systems. Identification of indole transport pathway through AcrB can be very helpful in understanding the drug efflux mechanism used by the MDR bacteria.

Clustering of Entanglement Points in Highly Strained Polymer Melts.

Polymer melts undergoing large deformation by elongation are studied by molecular dynamics simulations of bead–spring chains in melts. By applying a primitive path analysis to strongly deformed polymer melts, the role of topological constraints in highly entangled polymer melts is investigated and quantified. We show that the overall, large scale conformations of the primitive paths (PPs) of stretched chains follow affine deformation while the number and the distribution of entanglement points along the PPs do not. Right after deformation, PPs of chains retract in both directions parallel and perpendicular to the elongation. Upon further relaxation we observe a long-lived clustering of entanglement points. Together with the delayed relaxation time this leads to a metastable inhomogeneous distribution of topological constraints in the melts.

Small- and large-scale galactic conformity in SDSS DR7

Galactic conformity is the phenomenon whereby galaxy properties exhibit excess correlations across distance than that expected if these properties only depended on halo mass. We perform a comprehensive study of conformity at low redshift using a galaxy group catalogue from the SDSS DR7 spectroscopic sample. We study correlations both between central galaxies and their satellites (1-halo), and between central galaxies in separate haloes (2-halo). We use the quenched fractions and the marked correlation function (MCF), to probe for conformity in three galaxy properties, $(g-r)$ colour, specific star formation rate (sSFR), and morphology. We assess the statistical significance of conformity signals with a suite of mock galaxy catalogues that have no built-in conformity, but contain the same group-finding and mass assignment errors as the real data. In the case of 1-halo conformity, quenched fractions show strong signals at all group masses. However, these signals are equally strong in mock catalogues, indicating that the conformity signal is spurious and likely entirely caused by group-finding systematics, calling into question previous claims of 1-halo conformity detection. The MCF reveals a significant detection of radial segregation within massive groups, but no evidence of conformity. In the case of 2-halo conformity, quenched fractions show no significant evidence of conformity in colour or sSFR once compared with mock catalogues, but a clear signal using morphology. In contrast, the MCF reveals a small, yet highly significant signal for all three properties in low mass groups and scales of $0.8-4\ h^{-1}\textrm{Mpc}$, possibly representing the first robust detection of 2-halo conformity.

The large-scale effect of environment on galactic conformity

We use a volume-limited galaxy sample from the SDSS Data Release 7 to explore the dependence of galactic conformity on the large-scale environment, measured on $\sim$ 4 Mpc scales. We find that the star formation activity of neighbour galaxies depends more strongly on the environment than on the activity of their primary galaxies. In under-dense regions most neighbour galaxies tend to be active, while in over-dense regions neighbour galaxies are mostly passive, regardless of the activity of their primary galaxies. At a given stellar mass, passive primary galaxies reside in higher density regions than active primary galaxies, leading to the apparently strong conformity signal. The dependence of the activity of neighbour galaxies on environment can be explained by the corresponding dependence of the fraction of satellite galaxies. Similar results are found for galaxies in a semi-analytical model, suggesting that no new physics is required to explain the observed large-scale conformity.

Halo histories versus galaxy properties at z = 0 II: large-scale galactic conformity

Using group catalogs from the SDSS DR7, we attempt to measure galactic conformity in the local universe. We measure the quenched fraction of neighbor galaxies around isolated primary galaxies, dividing the isolated sample into star-forming and quiescent objects. We restrict our measurements to scales $>1$ Mpc to probe the correlations between the formation histories of distinct halos. Over the stellar mass range $10^{9.7} \le M_\ast/M_\odot \le 10^{10.9}$, we find minimal statistical evidence for conformity. We further compare these data to predictions of the halo age-matching model, in which the oldest galaxies are associated with the oldest halos at fixed $M_\ast$. For models with strong correlations between halo and stellar age, the conformity signal is too large to be consistent with the data. For weaker implementations of age-matching, galactic conformity is not a sensitive diagnostic of halo assembly bias, and would not produce a detectable signal in SDSS data. We reproduce the results of Kauffmann et al 2013, in which the star formation rates of neighbor galaxies are significantly reduced around primary galaxies when the primaries are themselves low star formers. However, we find this result is mainly driven by contamination in the isolation criterion, when using our group catalog to remove the small fraction of satellite galaxies in the sample, the conformity signal largely goes away. Lastly, we show that small conformity signals, i.e., 2-5% differences in the quenched fractions of neighbor galaxies, can be produced by mechanisms other than halo assembly bias. For example, if passive galaxies occupy more massive halos than star forming galaxies of the same stellar mass, a conformity signal that is consistent with recent measurements from PRIMUS (Berti et al 2016) can be produced.

Epigenetic remodeling in preimplantation embryos: cows are not big mice.

Epigenetic mechanisms allow the establishment and maintenance of multiple cellular phenotypes from a single genomic code. At the initiation of development, the oocyte and spermatozoa provide their fully differentiated chromatin that soon after fertilization undergo extensive remodeling, resulting in a totipotent state that can then drive cellular differentiation towards all cell types. These remodeling involves different epigenetic modifications, including DNA methylation, post-translational modifications of histones, non-coding RNAs, and large-scale chromatin conformation changes. Moreover, epigenetic remodeling is responsible for reprogramming somatic cells to totipotency upon somatic cell nuclear transfer/cloning, which is often incomplete and inefficient. Given that environmental factors, such as assisted reproductive techniques (ARTs), can affect epigenetic remodeling, there is interest in understanding the mechanisms driving these changes. We describe and discuss our current understanding of mechanisms responsible for the epigenetic remodeling that ensues during preimplantation development of mammals, presenting findings from studies of mouse embryos and when available comparing them to what is known for human and cattle embryos.

Large-scale correlations in gas traced by Mg ii absorbers around low-mass galaxies

Abstract The physical origin of the large-scale conformity in the colours and specific star formation rates of isolated low-mass central galaxies and their neighbours on scales in excess of 1 Mpc is still under debate. One possible scenario is that gas is heated over large scales by feedback from active galactic nuclei (AGNs), leading to coherent modulation of cooling and star formation between well-separated galaxies. In this Letter, the metal line absorption catalogue of Zhu & Ménard is used to probe gas out to large projected radii around a sample of a million galaxies with stellar masses ∼1010M⊙ and photometric redshifts in the range 0.4 < z < 0.8 selected from Sloan Digital Sky Survey imaging data. This galaxy sample covers an effective volume of 2.2 Gpc3. A statistically significant excess of Mg ii absorbers is present around the red-low-mass galaxies compared to their blue counterparts out to projected radii of 10 Mpc. In addition, the equivalent width distribution function of Mg ii absorbers around low-mass galaxies is shown to be strongly affected by the presence of a nearby (Rp < 2 Mpc) radio-loud AGNs out to projected radii of 5 Mpc.

Preheating of the Intergalactic Medium by Gravitational Collapse and Ultraviolet Background

Abstract The preheating of the intergalactic medium by structure collapse and ultraviolet background (UVB) is investigated in cosmological hydrodynamical simulations. When gravitational collapse is the sole heating mechanism, we find that (1) 60% and 45% of the IGM are heated up to S > 8 and 17 keV cm2, respectively, at z = 0, but the fractions drop rapidly to a few percent at z = 2; (2) the entropy of the circumhalo gas is higher than the virial entropy for more than 75% of the halos with masses since z = 2, but the fraction higher than the entropy, , required in the preventive model of galaxy formation is only 15%–20% for halos with at z = 0, and decreases as redshift increases; (3) assuming a metallicity of , the fraction of halos whose circumhalo gas has a cooling time longer than the Hubble time is merely 5%–10% at , and even less at for halos with ; and (4) gas in the filaments undergoes the strongest preheating. Furthermore, we show that the UVB cannot enhance the fraction of the IGM with , but can increase the fraction of low-mass halos ( ) having to ∼70% at z = 0 and that having to 15%–30% at . Our results indicate that preheating due to gravitational collapse and UVB is inadequate to fulfill the needs of the preventative model, especially for halos with . Nevertheless, these two mechanisms might cause large-scale galactic conformity.

On the evidence for large-scale galactic conformity in the local Universe

We re-examine the observational evidence for large-scale (4 Mpc) galactic conformity in the local Universe, as presented in Kauffmann et al. (2013). We show that a number of methodological features of their analysis act to produce a misleadingly high amplitude of the conformity signal. These include a weighting in favour of central galaxies in very high-density regions, the likely misclassification of satellite galaxies as centrals in the same high-density regions, and the use of medians to characterize bimodal distributions. We show that the large-scale conformity signal in Kauffmann et al. clearly originates from a very small number of central galaxies in the vicinity of just a few very massive clusters, whose effect is strongly amplified by the methodological issues that we have identified. Some of these 'centrals' are likely misclassified satellites, but some may be genuine centrals showing a real conformity effect. Regardless, this analysis suggests that conformity on 4 Mpc scales is best viewed as a relatively short-range effect (at the virial radius) associated with these very large neighbouring haloes, rather than a very long-range effect (at tens of virial radii) associated with the relatively low-mass haloes that host the nominal central galaxies in the analysis. A mock catalogue constructed from a recent semi-analytic model shows very similar conformity effects to the data when analysed in the same way, suggesting that there is no need to introduce new physical processes to explain galactic conformity on 4 Mpc scales.

Dissecting Conformational Features and Binding Mechanisms of Phenylalanine-Glycine Rich Nucleoporins

Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins (IPDs), constituting the selective barrier of the nuclear pore complex (NPC), which can be crossed by nuclear transport receptors (NTRs). How interaction of NTRs affects conformational features of FG-Nups to orchestrate nucleocytoplasmic transport remainsunclear. We previously showed that NTRs interact with FG-Nups with remarkably fast diffusion-limited kinetics, employing a set of multivalent interactions requiring no large-scale conformation changes. This ensures rapid yet specific nucleocytoplasmic transport via formation of a dynamic “fuzzy” complexes. Here we demonstrate that the binding of CRM1, an export NTR, can induce a conformational change in FG-Nup214. The affinity of this complex can be further modulated by RanGTP, which binds to CRM1. Kinetic measurements show that the binding of CRM1 with FG-Nup214 is very fast but slower than most other FG-Nups⋅NTRs interactions. These results suggest the formation of a structurally stable complex, which is different from the dynamic multivalent FG-Nup⋅NTR “fuzzy” complexes previously seen. However, a major question remains, if those studies are relevant to physiological conditions, since metazoan NPCs are highly glycosylated. We thus provide insight into the FG-Nup⋅NTR interaction mechanism of O-linked-N-acetylglycosamine modified FG-Nup214. We observed that glycosylation modulates the valency and interaction strength of Nup214⋅CRM1 complex, while retaining the binding mode of Nup214 and CRM1⋅RanGTP. Our results indicate the possibility that post-translational modifications of FG-Nups may add another layer of subtle regulation of FG-Nup functions. In summary, our findings highlight the layers of complexity involved in FG-Nup⋅NTR interactions. This brings us a step forward to decipher transport across the NPC from a molecular standpoint by directly interrogating details like their diversity, spatial localizations and dynamics.

Modeling and Analysis of Intercalant Effects on Circular DNA Conformation.

The large-scale conformation of DNA molecules plays a critical role in many basic elements of cellular functionality and viability. By targeting the structural properties of DNA, many cancer drugs, such as anthracyclines, effectively inhibit tumor growth but can also produce dangerous side effects. To enhance the development of innovative medications, rapid screening of structural changes to DNA can provide important insight into their mechanism of interaction. In this study, we report changes to circular DNA conformation from intercalation with ethidium bromide using all-atom molecular dynamics simulations and characterized experimentally by translocation through a silicon nitride solid-state nanopore. Our measurements reveal three distinct current blockade levels and a 6-fold increase in translocation times for ethidium bromide-treated circular DNA as compared to untreated circular DNA. We attribute these increases to changes in the supercoiled configuration hypothesized to be branched or looped structures formed in the circular DNA molecule. Further evidence of the conformational changes is demonstrated by qualitative atomic force microscopy analysis. These results expand the current methodology for predicting and characterizing DNA tertiary structure and advance nanopore technology as a platform for deciphering structural changes of other important biomolecules.

On the physical origin of galactic conformity

Correlations between the star formation rates (SFRs) of nearby galaxies (so-called galactic conformity) have been observed for projected separations up to 4 Mpc, an effect not predicted by current semi-analytic models. We investigate correlations between the mass accretion rates (dMvir/dt) of nearby halos as a potential physical origin for this effect. We find that pairs of host halos "know about" each others' assembly histories even when their present-day separation is greater than thirty times the virial radius of either halo. These distances are far too large for direct interaction between the halos to explain the correlation in their dMvir/dt. Instead, halo pairs at these distances reside in the same large-scale tidal environment, which regulates dMvir/dt for both halos. Larger halos are less affected by external forces, which naturally gives rise to a mass dependence of the halo conformity signal. SDSS measurements of galactic conformity exhibit a qualitatively similar dependence on stellar mass, including how the signal varies with distance. Based on the expectation that halo accretion and galaxy SFR are correlated, we predict the scale-, mass- and redshift-dependence of large-scale galactic conformity, finding that the signal should drop to undetectable levels by z > 1. These predictions are testable with current surveys to z ~ 1; confirmation would establish a strong correlation between dark matter halo accretion rate and central galaxy SFR.