scholarly journals PRDM16 establishes lineage-specific transcriptional program to promote temporal progression of neural progenitors in the mouse neocortex

2019 ◽  
Author(s):  
Li He ◽  
Jennifer Jones ◽  
Weiguo He ◽  
Bryan Bjork ◽  
Jiayu Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Radial Glia ◽  
Critical Role ◽  
Genomic Analysis ◽  
Chromatin Accessibility ◽  
Gene Expression Program ◽  
Projection Neurons ◽  
Specific Gene ◽  
Cortical Laminar ◽  
Expression Program

AbstractRadial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phases of neurogenesis in the mouse neocortex. Prdm16 mutant RG delays the timely progression of RG, leading to defective cortical laminar organization. We show that PRDM16 regulates expression of neuronal specification genes and a subset of genes that are dynamically expressed between mid-and late-neurogenesis. Our genomic analysis suggests that PRDM16 suppresses target gene expression through maintaining chromatin accessibility of permissive enhancers. Altogether, our results demonstrate a critical role of PRDM16 in establishing stage-specific gene expression program of RG during cortical neurogenesis. These findings also support a model where progenitor cells are primed with daughter cell gene expression program for rapid cell differentiation.

scholarly journals PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors

Development ◽  
2021 ◽  
Vol 148 (6) ◽  
Author(s):  
Li He ◽  
Jennifer Jones ◽  
Weiguo He ◽  
Bryan C. Bjork ◽  
Jiayu Wen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Radial Glia ◽  
Late Phase ◽  
Chromatin Accessibility ◽  
Neural Progenitors ◽  
Projection Neurons ◽  
Cell Cycle Regulators ◽  
Cell Diversity ◽  
Cortical Laminar

ABSTRACT Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.

Chromatin-Modifying Enzymes in T Cell Development

2020 ◽  
Vol 38 (1) ◽  
pp. 397-419
Author(s):  
Michael J. Shapiro ◽  
Virginia Smith Shapiro
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Biological Effects ◽  
Critical Role ◽  
T Cell Development ◽  
Regulation Of Gene Expression ◽  
Chromatin Accessibility ◽  
Cell Development ◽  
Specific Gene ◽  
Dynamic Regulation

T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.

scholarly journals The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program

2019 ◽  
Vol 124 (9) ◽  
pp. 1337-1349 ◽  
Author(s):  
Viktoria Kalna ◽  
Youwen Yang ◽  
Claire R. Peghaire ◽  
Karen Frudd ◽  
Rebecca Hannah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Expression Program ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Expression Program

scholarly journals A specific gene expression program triggered by Gram-positive bacteria in the cytosol

2004 ◽  
Vol 101 (31) ◽  
pp. 11386-11391 ◽  
Author(s):  
R. L. McCaffrey ◽  
P. Fawcett ◽  
M. O'Riordan ◽  
K.-D. Lee ◽  
E. A. Havell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Program ◽  
Specific Gene ◽  
Gram Positive ◽  
Specific Gene Expression ◽  
Gram Positive Bacteria ◽  
Expression Program

scholarly journals Bcl11b prevents catastrophic autoimmunity by controlling multiple aspects of a regulatory T cell gene expression program

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw0706 ◽  
Author(s):  
Syed Nurul Hasan ◽  
Amit Sharma ◽  
Sayantani Ghosh ◽  
Sung-Wook Hong ◽  
Sinchita Roy-Chowdhuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Immunological Tolerance ◽  
Gene Expression Program ◽  
Specific Gene ◽  
Molecular Features ◽  
Molecular Events ◽  
Cell Gene Expression ◽  
Genomic Recruitment ◽  
Expression Program

Foxp3 and its protein partners establish a regulatory T (Treg) cell transcription profile and promote immunological tolerance. However, molecular features contributing to a Treg-specific gene expression program are still incompletely understood. We find that the transcription factor Bcl11b is a prominent Foxp3 cofactor with multifaceted functions in Treg biology. Optimal genomic recruitment of Foxp3 and Bcl11b is critically interdependent. Genome-wide occupancy studies coupled with gene expression profiling reveal that Bcl11b, in association with Foxp3, is primarily responsible in establishing a Treg-specific gene activation program. Furthermore, Bcl11b restricts misdirected recruitment of Foxp3 to sites, which would otherwise result in an altered Treg transcriptome profile. Consequently, Treg-specific ablation of Bcl11b results in marked breakdown of immune tolerance, leading to aggressive systemic autoimmunity. Our study provides previously underappreciated mechanistic insights into molecular events contributing to basic aspects of Treg function. Furthermore, it establishes a therapeutic target with potential implications in autoimmunity and cancer.

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