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1.
Nucleic Acids Res ; 45(6): 3059-3067, 2017 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-27940560

RESUMEN

Communication between distantly spaced genomic regions is one of the key features of gene regulation in eukaryotes. Chromatin per se can stimulate efficient enhancer-promoter communication (EPC); however, the role of chromatin structure and dynamics in this process remains poorly understood. Here we show that nucleosome spacing and the presence of nucleosome-free DNA regions can modulate chromatin structure/dynamics and, in turn, affect the rate of EPC in vitro and in silico. Increasing the length of internucleosomal linker DNA from 25 to 60 bp results in more efficient EPC. The presence of longer nucleosome-free DNA regions can positively or negatively affect the rate of EPC, depending upon the length and location of the DNA region within the chromatin fiber. Thus the presence of histone-free DNA regions can differentially affect the efficiency of EPC, suggesting that gene regulation over a distance could be modulated by changes in the length of internucleosomal DNA spacers.


Asunto(s)
Cromatina/química , ADN/química , Elementos de Facilitación Genéticos , Nucleosomas/metabolismo , Regiones Promotoras Genéticas , Animales , Pollos , ADN/metabolismo
2.
Biophys J ; 112(3): 416-426, 2017 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-27955889

RESUMEN

One of the critical unanswered questions in genome biophysics is how the primary sequence of DNA bases influences the global properties of very-long-chain molecules. The local sequence-dependent features of DNA found in high-resolution structures introduce irregularities in the disposition of adjacent residues that facilitate the specific binding of proteins and modulate the global folding and interactions of double helices with hundreds of basepairs. These features also determine the positions of nucleosomes on DNA and the lengths of the interspersed DNA linkers. Like the patterns of basepair association within DNA, the arrangements of nucleosomes in chromatin modulate the properties of longer polymers. The intrachromosomal loops detected in genomic studies contain hundreds of nucleosomes, and given that the simulated configurations of chromatin depend on the lengths of linker DNA, the formation of these loops may reflect sequence-dependent information encoded within the positioning of the nucleosomes. With knowledge of the positions of nucleosomes on a given genome, methods are now at hand to estimate the looping propensities of chromatin in terms of the spacing of nucleosomes and to make a direct connection between the DNA base sequence and larger-scale chromatin folding.


Asunto(s)
ADN/química , ADN/genética , Animales , Emparejamiento Base , Secuencia de Bases , Cromatina/química , Cromatina/genética , Genómica , Humanos , Nucleosomas/genética
3.
J Mol Biol ; 433(18): 167121, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34192585

RESUMEN

While nucleosomes are dynamic entities that must undergo structural deformations to perform their functions, the general view from available high-resolution structures is a largely static one. Even though numerous examples of twist defects have been documented, the DNA wrapped around the histone core is generally thought to be overtwisted. Analysis of available high-resolution structures from the Protein Data Bank reveals a heterogeneous distribution of twist along the nucleosomal DNA, with clear patterns that are consistent with the literature, and a significant fraction of structures that are undertwisted. The subtle differences in nucleosomal DNA folding, which extend beyond twist, have implications for nucleosome disassembly and modeled higher-order structures. Simulations of oligonucleosome arrays built with undertwisted models behave very differently from those constructed from overtwisted models, in terms of compaction and inter-nucleosome contacts, introducing configurational changes equivalent to those associated with 2-3 base-pair changes in nucleosome spacing. Differences in the nucleosomal DNA pathway, which underlie the way that DNA enters and exits the nucleosome, give rise to different nucleosome-decorated minicircles and affect the topological mix of configurational states.


Asunto(s)
Ensamble y Desensamble de Cromatina , ADN/química , Histonas/química , Conformación de Ácido Nucleico , Nucleosomas/química , Modelos Moleculares
4.
Epigenomics ; 9(9): 1219-1231, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28799793

RESUMEN

Enhancers are regulatory DNA sequences that can activate transcription over large distances. Recent studies have revealed the widespread role of distant activation in eukaryotic gene regulation and in the development of various human diseases, including cancer. Here we review recent progress in the field, focusing on new experimental and computational approaches that quantify the role of chromatin structure and dynamics during enhancer-promoter interactions in vitro and in vivo.


Asunto(s)
Elementos de Facilitación Genéticos , Epigénesis Genética , Animales , Cromatina/genética , Cromatina/metabolismo , Genómica/métodos , Humanos
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