Why are so many MLL lysine methyltransferases required for normal mammalian development? DOI Creative Commons
Nicholas T. Crump, Thomas A. Milne

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(15), P. 2885 - 2898

Published: May 16, 2019

The mixed lineage leukemia (MLL) family of proteins became known initially for the link its founding member. Over decades, MLL has been recognized as an important class histone H3 lysine 4 (H3K4) methyltransferases that control key aspects normal cell physiology and development. Here, we provide a brief history discovery study this proteins. We address two main questions: why are there so many H3K4 in mammals; is methylation their function?

Language: Английский

The molecular principles of gene regulation by Polycomb repressive complexes DOI
Neil P. Blackledge, Robert J. Klose

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(12), P. 815 - 833

Published: Aug. 16, 2021

Language: Английский

Citations

338

Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation DOI
Marc A. Morgan, Ali Shilatifard

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(12), P. 1271 - 1281

Published: Nov. 30, 2020

Language: Английский

Citations

294

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer DOI Open Access
Adrian P. Bracken, Gerard L. Brien, C. Peter Verrijzer

et al.

Genes & Development, Journal Year: 2019, Volume and Issue: 33(15-16), P. 936 - 959

Published: May 23, 2019

Changes in chromatin structure mediated by ATP-dependent nucleosome remodelers and histone modifying enzymes are integral to the process of gene regulation. Here, we review roles SWI/SNF (switch/sucrose nonfermenting) NuRD (nucleosome remodeling deacetylase) Polycomb system regulation cancer. First, discuss basic molecular mechanism remodeling, how this controls transcription. Next, provide an overview functional organization biochemical activities SWI/SNF, NuRD, complexes. We describe how, metazoans, balance these is central proper expression cellular identity during development. Whereas counteracts Polycomb, facilitates repression on chromatin. Finally, disruptions regulatory equilibrium contribute oncogenesis, new insights into biological functions Polycombs opening avenues for therapeutic interventions a broad range cancer types.

Language: Английский

Citations

157

Hox genes in development and beyond DOI Open Access
Katharine A. Hubert, Deneen M. Wellik

Development, Journal Year: 2023, Volume and Issue: 150(1)

Published: Jan. 1, 2023

ABSTRACT Hox genes encode evolutionarily conserved transcription factors that are essential for the proper development of bilaterian organisms. unique because they spatially and temporally regulated during in a manner is dictated by their tightly linked genomic organization. Although genetic function embryonic has been interrogated, less known about how these regulate downstream to direct morphogenetic events. Moreover, continued expression at postnatal adult stages highlights crucial roles throughout life an organism. Here, we provide overview genes, highlighting evolutionary history, organization this impacts regulation expression, what protein structure, deployment beyond.

Language: Английский

Citations

55

A high-quality Ixodes scapularis genome advances tick science DOI
Sandip De, Sarah B. Kingan,

Chrysoula Kitsou

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 301 - 311

Published: Jan. 19, 2023

Language: Английский

Citations

54

Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts DOI Creative Commons
Stephen S. Gisselbrecht,

Alexandre Palagi,

Jesse V. Kurland

et al.

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(2), P. 324 - 337.e8

Published: Nov. 5, 2019

Language: Английский

Citations

114

Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming DOI
Mitzi I. Kuroda, Hyuckjoon Kang, Sandip De

et al.

Annual Review of Biochemistry, Journal Year: 2020, Volume and Issue: 89(1), P. 235 - 253

Published: Jan. 13, 2020

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of genome by chromatin proteins, histone modifications, and differential compaction largely sufficient to reveal locations genes their activity states. The Polycomb Group (PcG) Trithorax (TrxG) proteins are central players in this cell type-specific organization. PcG function was originally viewed as being solely repressive irreversible, observed at homeotic loci flies mammals. it now clear that modular reversible essential most developmental genes. Focusing mainly on recent advances, we review evidence for how TrxG change dynamically during type transitions. ability implement transcriptional programming with exquisite fidelity normal development.

Language: Английский

Citations

113

Phase separation by the polyhomeotic sterile alpha motif compartmentalizes Polycomb Group proteins and enhances their activity DOI Creative Commons

Elias Seif,

Jin Joo Kang,

Charles Sasseville

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 5, 2020

Polycomb Group (PcG) proteins organize chromatin at multiple scales to regulate gene expression. A conserved Sterile Alpha Motif (SAM) in the Repressive Complex 1 (PRC1) subunit Polyhomeotic (Ph) has been shown play an important role compaction and large-scale organization. Ph SAM forms helical head tail polymers, SAM-SAM interactions between chromatin-bound Ph/PRC1 are believed compact mediate long-range interactions. To understand underlying mechanism, here we analyze effects of on vitro. We find that incubation or DNA with a truncated protein containing results formation concentrated, phase-separated condensates. SAM-dependent condensates can recruit PRC1 from extracts enhance ubiquitin ligase activity towards histone H2A. show overexpression intact increases ubiquitylated H2A cells. Thus, SAM-induced phase separation, context Ph, into biochemical compartments facilitate modification.

Language: Английский

Citations

98

Regulation of growth and cell fate during tissue regeneration by the two SWI/SNF chromatin-remodeling complexes of Drosophila DOI Open Access
Yuan Tian, Rachel K. Smith-Bolton

Genetics, Journal Year: 2020, Volume and Issue: 217(1)

Published: Dec. 22, 2020

Abstract To regenerate, damaged tissue must heal the wound, regrow to proper size, replace correct cell types, and return normal gene-expression program. However, mechanisms that temporally spatially control activation or repression of important genes during regeneration are not fully understood. determine role chromatin modifiers play in regulating gene expression after damage, we induced ablation Drosophila melanogaster imaginal wing discs, screened for regulators required epithelial regeneration. Here, show many these indeed promoting constraining Specifically, two SWI/SNF chromatin-remodeling complexes distinct roles different aspects The PBAP complex regulates regenerative growth developmental timing, is JNK signaling targets promoter Myc. By contrast, BAP ensures patterning fate by stabilizing posterior engrailed. Thus, both essential regeneration, but they fate.

Language: Английский

Citations

75

Role of Histone Post-Translational Modifications in Inflammatory Diseases DOI Creative Commons
Yingying Lin, Ting Qiu, Guifeng Wei

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 24, 2022

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer’s disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel virus-associated diseases. Epigenetic mechanisms have been demonstrated play key role in regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, non-coding RNA expression; among these, modifications embrace various post-modifications including acetylation, phosphorylation, ubiquitination, ADP ribosylation. This review focuses on significant progression providing potential target clinical therapy inflammation-associated

Language: Английский

Citations

58