A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation

Tatiana Gerasimova; Changying Guo; Amalendu Ghosh; Xiang Qiu; Lindsey Montefiori; Jiyoti Verma-Gaur; Nancy M. Choi; Ann J. Feeney; Ranjan Sen

doi:10.1101/gad.263871.115.

A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation

Tatiana Gerasimova, Changying Guo, Amalendu Ghosh, Xiang Qiu, Lindsey Montefiori, Jiyoti Verma-Gaur, Nancy M. Choi, Ann J. Feeney, Ranjan Sen

Research output: Contribution to journal › Article › peer-review

Abstract

Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (V_H) gene segments. The 5′ and 3′ domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.

Original language	English (US)
Pages (from-to)	1683-1695
Number of pages	13
Journal	Genes & development
Volume	29
Issue number	16
DOIs	https://doi.org/10.1101/gad.263871.115.
State	Published - Aug 15 2015
Externally published	Yes

Keywords

Architectural proteins
Chromosome conformation
Looping

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.263871.115.

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title = "A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation",

abstract = "Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (VH) gene segments. The 5′ and 3′ domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.",

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AU - Gerasimova, Tatiana

AU - Guo, Changying

AU - Ghosh, Amalendu

AU - Qiu, Xiang

AU - Montefiori, Lindsey

AU - Verma-Gaur, Jiyoti

AU - Choi, Nancy M.

AU - Feeney, Ann J.

AU - Sen, Ranjan

PY - 2015/8/15

Y1 - 2015/8/15

N2 - Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (VH) gene segments. The 5′ and 3′ domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.

AB - Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (VH) gene segments. The 5′ and 3′ domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.

KW - Architectural proteins

KW - Chromosome conformation

KW - Looping

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A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation

Abstract

Keywords

ASJC Scopus subject areas

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