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Shankar, G.

Publications and source records attributed to Shankar, G..

3 recordsLinked to original sources

Environmental sensing capacity predicts bacterial ecological strategies and environmental preferences

The ability to sense environmental variation is a prerequisite for ecological success. Sensor domains enable bacteria to detect nutrients, neighboring organisms, and physicochemical conditions, but whether variation in these sensing systems reflects ecological specialization remains unresolved. Here, we analyzed sensor domains across 51,343 bacterial genomes and 255 soil metagenomes spanning a climatic gradient to determine whether sensory repertoires encode bacterial ecological strategies and environmental preferences. Sensory repertoires exhibited strong phylogenetic conservatism and revealed signatures of genome streamlining, indicating that environmental sensing reflects trade-offs associated with maintaining sensory complexity. Taxa occupying environmentally heterogeneous habitats, particularly free-living aerobic generalists, encoded the largest sensory repertoires, consistent with selection for expanded environmental information processing. To link sensory function with ecological adaptation, we mapped experimentally-characterized ligand-binding motifs (LBMs) across genomes and metagenomes. Distinct LBM profiles discriminated host-associated and free-living taxa, aerobic and anaerobic lineages, and generalists and non-generalists, revealing a tight coupling between sensory capacity and ecological strategy. Across soil communities, motifs associated with osmoprotection and oxygen sensing were consistently enriched under increasing aridity, linking sensory function to environmental filtering in natural ecosystems. These findings identify environmental sensing as an important organizational axis of bacterial trait-based ecology that integrates evolutionary history, ecological lifestyle, and adaptation to local conditions. Environmental sensing should be considered for predicting microbial niches and responses to environmental change.

ecology

Feedback Regulation between Initiation and Maturation Networks Orchestrates the Chromatin Dynamics of Epidermal Lineage Commitment

Tissue development results from lineage-specific transcription factors (TF) programming a dynamic chromatin landscape through progressive cell fate transitions. Here, we interrogate the epigenomic landscape during epidermal differentiation and create an inference network that ranks the coordinate effects of TF-accessible regulatory element-target gene expression triplets on lineage commitment. We discover two critical transition periods: surface ectoderm initiation and keratinocyte maturation, and identify TFAP2C and p63 as lineage initiation and maturation factors, respectively. Surprisingly, we find that TFAP2C, and not p63, is sufficient to initiate surface ectoderm differentiation, with TFAP2C-initiated progenitor cells capable of maturing into functional keratinocytes. Mechanistically, TFAP2C primes the surface ectoderm chromatin landscape and induces p63 expression and binding sites, thus allowing maturation factor p63 to positively auto-regulate its expression and close a subset of the TFAP2C-initiated early program. Our work provides a general framework to infer TF networks controlling chromatin transitions that will facilitate future regenerative medicine advances.

cell biology

Morphogen-Lineage Selector Interactions During Surface Epithelial Commitment

Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine1-3, yet conversion of hESCs into tissues such as keratinocytes requires a better understanding of epigenetic interactions between the inductive morphogens retinoic acid (RA) and bone morphogenetic protein 4 (BMP), and the master regulator p634,5. Here we develop a robust, defined, keratinocyte differentiation system, and use a multi-dimensional genomics approach to interrogate the contributions of the morphogens and lineage selector to chromatin dynamics during early surface ectoderm commitment. In stark contrast to other master regulators6-9, we find using p63 gain and loss of function hESC lines, that p63 effects major transcriptional changes only after morphogenetic action. Morphogens alter chromatin accessibility and histone modifications, establishing an epigenetic landscape for p63 to modify. In turn, p63 closes chromatin accessibility and promotes the accumulation of repressive H3K27me3 histone modifications at sites distal to where it binds. Surprisingly, cohesin HiChIP10 visualization of genome-wide chromosome conformation reveals that both p63 and the morphogens contribute to dynamic long-range genomic interactions that increase the probability of negative transcriptional regulation at p63 target loci. p63-regulated accessibility, not H3K27me3 deposition, appears to drive early transcriptional changes. We illustrate morphogen-selector interactions by studying p63 negative feedback regulation of TFAP2Ci11, whereby disruption of the single p63 binding site results in a loss of p63-mediated transcriptional control and dramatic increases in TFAP2C and p63 expression. Our study reveals the unexpected dependency of p63 on morphogenetic signaling to control long-range chromatin interactions during tissue specification and provides novel insights into how master regulators specify diverse morphological outcomes.

genetics