Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules.
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.
Hu
Qidong
Q
Department of Medicine, Howard Hughes Medical Institute,
Kwon
Young-Soo
YS
Nunez
Esperanza
E
Cardamone
Maria Dafne
MD
Hutt
Kasey R
KR
Ohgi
Kenneth A
KA
Garcia-Bassets
Ivan
I
Rose
David W
DW
Glass
Christopher K
CK
Rosenfeld
Michael G
MG
Fu
Xiang-Dong
XD
D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology; D002843:Chromatin / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D053263:Gene Regulatory Networks / Q000502:physiology*; D056466:Histone Demethylases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D047628:Estrogen Receptor alpha; D004967:Estrogens; C416830:GREB1 protein, human; D009363:Neoplasm Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating