Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules.

Abstract:

:Although the role of liganded nuclear receptors in mediating coactivator/corepressor exchange is well-established, little is known about the potential regulation of chromosomal organization in the 3-dimensional space of the nucleus in achieving integrated transcriptional responses to diverse signaling events. Here, we report that ligand induces rapid interchromosomal interactions among specific subsets of estrogen receptor alpha-bound transcription units, with a dramatic reorganization of nuclear territories, which depends on the actions of nuclear actin/myosin-I machinery and dynein light chain 1. The histone lysine demethylase, LSD1, is required for these ligand-induced interactive loci to associate with distinct interchromatin granules, long thought to serve as "storage" sites for the splicing machinery, some critical transcription elongation factors, and various chromatin remodeling complexes. We demonstrate that this 2-step nuclear rearrangement is essential for achieving enhanced, coordinated transcription of nuclear receptor target genes.

authors

Hu Q,Kwon YS,Nunez E,Cardamone MD,Hutt KR,Ohgi KA,Garcia-Bassets I,Rose DW,Glass CK,Rosenfeld MG,Fu XD

doi

10.1073/pnas.0810634105

subject

Has Abstract

pub_date

2008-12-09 00:00:00

pages

19199-204

issue

49

eissn

0027-8424

issn

1091-6490

pii

0810634105

journal_volume

105

pub_type

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