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Venkata, N. C.

Publications and source records attributed to Venkata, N. C..

3 recordsLinked to original sources

HSF1-dependent, long-range directional HSPA1 gene motion to nuclear speckles is coupled to DDX39B condensate dynamics

Approximately 5-10% of the genome, enriched [~]10-fold in the most highly active genes, positions near deterministically within several hundred nm of nuclear speckles (NS). This includes the HSPA1 locus, among the most strongly NS-associated genes. Here we address how HSPA1 endogenous genes and transgenes stably position adjacent to the nuclear speckle periphery, facilitating their gene expression amplification. Live-cell imaging demonstrates a transcription-dependent speckle-anchoring of HSPA1 genes. Removal of this anchoring reveals sustained, long-range, curvilinear oscillations of the HSPA1 genes away from and back to nuclear speckles or between nuclear speckles. Curvilinear transgene movements are dependent on the transcription factor HSF1, largely independent of nuclear actin or cohesin, but unexpectedly spatially and temporally correlated with DDX39B condensate dynamics and dependent on DDX39B protein levels. We propose that stable nuclear speckle association of HSPA1 results from combining metastable speckle anchoring with constitutive, restorative long-range chromosome movements driven by DDX39B condensate dynamics.

cell biology↗

Highly active chromosome regions preferentially associate with two perispeckle networks that partition the interchromatin space

A subset of highly active chromosomal "hot zones" reproducibly positions adjacent to nuclear speckles (NS). Genes within these regions amplify their expression only with NS contact. However, gene expression differences inversely correlate with differences in NS distance, genome-wide. We hypothesized the existence of additional gene expression "niches" away from, but spatially correlated with, NS. Here we report the identification of two dynamic perispeckle patterns of protein concentrations extending outwards from NS and persisting even after NS are eliminated. Highly active chromosome regions which weakly associate with NS instead show close, NS-independent association with these perispeckle patterns. Additionally, transcripts from model intron-containing versus intronless genes associate differentially with these two patterns. While genes within NS-associated genomic regions are predominantly downregulated upon NS depletion, genes associated with perispeckle patterns are biased towards upregulation. We suggest the interchromatin space is partitioned into additional gene expression "niches"- surrounding and extending from NS - that may be involved in mRNA and gene dynamics.

cell biology↗

Nonrandom interchromatin trafficking through dynamic multiphase speckle connections

Nuclear speckles (NS) enhance the expression of NS-associated genes, possibly by elevating local levels of factors involved in multiple steps of gene expression. While dozens of large NS are distributed throughout interchromatin regions, the extent to which NS components dynamically redistribute between NS to adjust to local physiological demands remains unknown. Here we used live-cell imaging of endogenous NS proteins to identify an interchromatin network of connections that functionally link NS throughout the nucleus. Over timescales ranging from tens of seconds to minutes, NS material undergoes bulk transfer through these connections. Multiphase NS-connecting structures form through the dynamic juxtapositions of multiple NS component phases. Each phase exhibits distinct yet recurrent viscoelastic dynamics, but together, they integrate into a more stable, multiphase, NS-connecting structure in an ATP-and transcription-dependent manner. Our findings reveal the existence of a cellular mechanism that facilitates coordinated inter-NS protein trafficking through multiphase connections.

cell biology↗