Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories

Abstract

differentiation and concomitant gene expression, we found that co-expressed genes were closer together. In addition, we found that genes in the same 1-μm-diameter neighborhood associated with either the same splicing speckle or to a lesser extent with the same transcription factory. Dispersal of speckles by overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2 led to a significant drop in the number of genes in shared neighborhoods. We demonstrate quantitatively that the frequencies of speckle and factory sharing can be explained by assuming stochastic selection of a nuclear body within a restricted sub-volume defined by the original global gene positioning present prior to gene expression. We conclude that the spatial organization of these genes is a two-step process in which transcription-induced association with nuclear bodies enhances and refines a pre-existing global organization.

Contribution of 3D Chromatin Architecture to the Maintenance of Pluripotency

“…This is consistent with numerous studies linking transcriptional co-regulation to spatial clustering of the relevant genes and their cis-regulatory elements [26][27][28][29][30][31][32] around the nucleoplasmic supra-molecular entities that harbor most nuclear transcription-around transcription factories [19].…”

Dynamics of the association of heat shock protein HSPA6 (Hsp70B’) and HSPA1A (Hsp70–1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells

“…The FRAP data suggests that HSPA6 exhibits a unique feature not observed for HSPA1A, namely a rapid and highly dynamic exchange with perispeckles, which have been characterized as transcription sites (Brown et al 2008;Spector and Lamond 2011;Rieder et al 2012;Rieder et al 2014). The presence of HSPA6 in the human genome could provide human neuronal cells with a highly dynamic mechanism for transcriptional recovery after stressful stimuli.…”

“…HSPA6, but not HSPA1A, associated with bright star-like foci located at the periphery of nuclear speckles following thermal stress. These perispeckles are sites of active mRNA transcription that have been characterized as Btranscription factories^ (Brown et al 2008;Spector and Lamond 2011;Rieder et al 2012;Rieder et al 2014). The unique localization of HSPA6, but not HSPA1A, to perispeckles, suggests that HSPA6 may be associated with the recovery of transcription in human neuronal cells after inhibition by stressful stimuli (Allen et al 2004;Hieda et al 2005;Espinoza et al 2007;Yakovchuk et al 2009).…”

“…4c). These perispeckles are sites of active messenger RNA (mRNA) transcription that have been termed Btranscription factories^ (Brown et al 2008;Spector and Lamond 2011;Rieder et al 2012;Rieder et al 2014). The unique localization of HSPA6, but not HSPA1A, at the periphery of nuclear speckles suggested that this little studied member of the HSPA family, which is not present in current animal models of neurodegenerative diseases, is associated with the recovery of transcription in neuronal cells after stressful stimuli.…”

“…Later in the recovery from neuronal stress, HSPA6, but not HSPA1A, localized to the periphery of nuclear speckles (perispeckles) that have been characterized as transcription sites (Brown et al 2008;Spector and Lamond 2011;Rieder et al 2012;Rieder et al 2014). FRAP revealed that the stressinduced interaction of HSPA6 with perispeckles displayed the greatest dynamism compared to the association of HSPA6 and HSPA1A with other stress-sensitive cytoplasmic and nuclear structures.…”