Pioneer Factors and Architectural Proteins Mediating Embryonic Expression Signatures in Cancer

Chromatin structure is critical for gene expression and many other cellular processes. In Arabidopsis thaliana, the floral repressor FLC adopts a self-loop chromatin structure via bridging of its flanking regions. This local gene loop is necessary for active FLC expression. However, the molecular mechanism underlying the formation of this class of gene loops is unknown. Here, we report the characterization of a group of linker histone-like proteins, named the GH1-HMGA family in Arabidopsis, which act as chromatin architecture modulators. We demonstrate that these family members redundantly promote the floral transition through the repression of FLC. A genome-wide study revealed that this family preferentially binds to the 5′ and 3′ ends of gene bodies. The loss of this binding increases FLC expression by stabilizing the FLC 5′ to 3′ gene looping. Our study provides mechanistic insights into how a family of evolutionarily conserved proteins regulates the formation of local gene loops.

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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity

eLife ◽

10.7554/elife.41266 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 14

Author(s):

Jeehae Park ◽

Javier Estrada ◽

Gemma Johnson ◽

Ben J Vincent ◽

Chiara Ricci-Tam ◽

...

Keyword(s):

Expression Pattern ◽

Molecular Mechanisms ◽

Regulatory Function ◽

Multiple Sources ◽

Pairwise Interactions ◽

Histone Modifiers ◽

Boundary Location ◽

Pioneer Factors ◽

Gene Regulatory ◽

Cis And Trans

Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, Mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. Comparing our results to theory reveals how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.

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Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture

Nucleic Acids Research ◽

10.1093/nar/gkw1114 ◽

2016 ◽

Vol 45 (4) ◽

pp. 1714-1730 ◽

Cited By ~ 71

Author(s):

Caelin Cubeñas-Potts ◽

M. Jordan Rowley ◽

Xiaowen Lyu ◽

Ge Li ◽

Elissa P. Lei ◽

...

Keyword(s):

Chromatin Interactions ◽

Architectural Proteins ◽

3D Architecture

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Nucleoid-associated proteins in Crenarchaea

Biochemical Society Transactions ◽

10.1042/bst0390116 ◽

2011 ◽

Vol 39 (1) ◽

pp. 116-121 ◽

Cited By ~ 14

Author(s):

Rosalie P.C. Driessen ◽

Remus Th. Dame

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Structural Effect ◽

Chromatin Organization ◽

Large Set ◽

Chromosomal Dna ◽

Amino Acid Sequence Level ◽

Generic Level ◽

Architectural Proteins ◽

Associated Proteins

Architectural proteins play an important role in compacting and organizing the chromosomal DNA in all three kingdoms of life (Eukarya, Bacteria and Archaea). These proteins are generally not conserved at the amino acid sequence level, but the mechanisms by which they modulate the genome do seem to be functionally conserved across kingdoms. On a generic level, architectural proteins can be classified based on their structural effect as DNA benders, DNA bridgers or DNA wrappers. Although chromatin organization in archaea has not been studied extensively, quite a number of architectural proteins have been identified. In the present paper, we summarize the knowledge currently available on these proteins in Crenarchaea. By the type of architectural proteins available, the crenarchaeal nucleoid shows similarities with that of Bacteria. It relies on the action of a large set of small, abundant and generally basic proteins to compact and organize their genome and to modulate its activity.

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XIST RNA: a window into the broader role of RNA in nuclear chromosome architecture

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0360 ◽

2017 ◽

Vol 372 (1733) ◽

pp. 20160360 ◽

Cited By ~ 13

Author(s):

K. M. Creamer ◽

J. B. Lawrence

Keyword(s):

X Chromosome ◽

Chromatin Condensation ◽

Higher Order ◽

Chromosome Architecture ◽

Genome Wide ◽

Xist Rna ◽

Architectural Proteins ◽

Mary Lyon ◽

Attachment Factor

XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoring XIST , but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact with XIST RNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA ‘coats’ euchromatin and may impact chromosome architecture in a manner opposite of XIST . A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

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HMGA Proteins in Stemness and Differentiation of Embryonic and Adult Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21010362 ◽

2020 ◽

Vol 21 (1) ◽

pp. 362 ◽

Cited By ~ 9

Author(s):

Silvia Parisi ◽

Silvia Piscitelli ◽

Fabiana Passaro ◽

Tommaso Russo

Keyword(s):

Experimental Data ◽

Stem Cells ◽

Cell Fate ◽

Adult Stem Cells ◽

Regulation Of Gene Expression ◽

Embryonic Stem ◽

Adult Stem Cell ◽

Mouse Development ◽

Architectural Proteins ◽

Numerous Experimental Data

HMGA1 and HMGA2 are chromatin architectural proteins that do not have transcriptional activity per se, but are able to modify chromatin structure by interacting with the transcriptional machinery and thus negatively or positively regulate the transcription of several genes. They have been extensively studied in cancer where they are often found to be overexpressed but their functions under physiologic conditions have still not been completely addressed. Hmga1 and Hmga2 are expressed during the early stages of mouse development, whereas they are not detectable in most adult tissues. Hmga overexpression or knockout studies in mouse have pointed to a key function in the development of the embryo and of various tissues. HMGA proteins are expressed in embryonic stem cells and in some adult stem cells and numerous experimental data have indicated that they play a fundamental role in the maintenance of stemness and in the regulation of differentiation. In this review, we discuss available experimental data on HMGA1 and HMGA2 functions in governing embryonic and adult stem cell fate. Moreover, based on the available evidence, we will aim to outline how HMGA expression is regulated in different contexts and how these two proteins contribute to the regulation of gene expression and chromatin architecture in stem cells.

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