TY - JOUR
T1 - Drosophila MCRS2 associates with RNA polymerase II complexes to regulate transcription
AU - Andersen, Ditte Skovaa
AU - Raja, Sunil Jayaramaiah
AU - Colombani, Julien
AU - Shaw, Rachael Louise
AU - Langton, Paul Francis
AU - Akhtar, Asifa
AU - Tapon, Nicolas
PY - 2010/10
Y1 - 2010/10
N2 - Drosophila MCRS2 (dMCRS2; MCRS2/MSP58 and its splice variant MCRS1/p78 in humans) belongs to a family of forkhead-associated (FHA) domain proteins. Whereas human MCRS2 proteins have been associated with a variety of cellular processes, including RNA polymerase I transcription and cell cycle progression, dMCRS2 has been largely uncharacterized. Recent data show that MCRS2 is purified as part of a complex containing the histone acetyltransferase MOF (males absent on first) in both humans and flies. MOF mediates H4K16 acetylation and regulates the expression of a large number of genes, suggesting that MCRS2 could also have a function in transcription regulation. Here, we show that dMCRS2 copurifies with RNA polymerase II (RNAP II) complexes and localizes to the 5' ends of genes. Moreover, dMCRS2 is required for optimal recruitment of RNAP II to the promoter regions of cyclin genes. In agreement with this, dMCRS2 is required for normal levels of cyclin gene expression. We propose a model whereby dMCRS2 promotes gene transcription by facilitating the recruitment of RNAP II preinitiation complexes (PICs) to the promoter regions of target genes.
AB - Drosophila MCRS2 (dMCRS2; MCRS2/MSP58 and its splice variant MCRS1/p78 in humans) belongs to a family of forkhead-associated (FHA) domain proteins. Whereas human MCRS2 proteins have been associated with a variety of cellular processes, including RNA polymerase I transcription and cell cycle progression, dMCRS2 has been largely uncharacterized. Recent data show that MCRS2 is purified as part of a complex containing the histone acetyltransferase MOF (males absent on first) in both humans and flies. MOF mediates H4K16 acetylation and regulates the expression of a large number of genes, suggesting that MCRS2 could also have a function in transcription regulation. Here, we show that dMCRS2 copurifies with RNA polymerase II (RNAP II) complexes and localizes to the 5' ends of genes. Moreover, dMCRS2 is required for optimal recruitment of RNAP II to the promoter regions of cyclin genes. In agreement with this, dMCRS2 is required for normal levels of cyclin gene expression. We propose a model whereby dMCRS2 promotes gene transcription by facilitating the recruitment of RNAP II preinitiation complexes (PICs) to the promoter regions of target genes.
KW - Animals
KW - Animals, Genetically Modified
KW - Blotting, Western
KW - Cell Proliferation
KW - Cells, Cultured
KW - Cyclins/genetics
KW - Drosophila Proteins/genetics
KW - Drosophila melanogaster/cytology
KW - Green Fluorescent Proteins/genetics
KW - Histone Acetyltransferases/genetics
KW - Mutation
KW - Nuclear Proteins/genetics
KW - Promoter Regions, Genetic/genetics
KW - Protein Binding
KW - RNA Interference
KW - RNA Polymerase II/metabolism
KW - Transcription, Genetic
U2 - 10.1128/mcb.01586-09
DO - 10.1128/mcb.01586-09
M3 - Journal article
C2 - 20679484
SN - 0270-7306
VL - 30
SP - 4744
EP - 4755
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 19
ER -