@article {Carvalho2013,
	title = {Histone methyltransferase SETD2 coordinates FACT recruitment with nucleosome dynamics during transcription},
	journal = {Nucleic acids research},
	volume = {41},
	number = {5},
	year = {2013},
	note = {<p>n/a</p>
},
	pages = {2881{\textendash}93},
	abstract = {<p>Histone H3 of nucleosomes positioned on active genes is trimethylated at Lys36 (H3K36me3) by the SETD2 (also termed KMT3A/SET2 or HYPB) methyltransferase. Previous studies in yeast indicated that H3K36me3 prevents spurious intragenic transcription initiation through recruitment of a histone deacetylase complex, a mechanism that is not conserved in mammals. Here, we report that downregulation of SETD2 in human cells leads to intragenic transcription initiation in at least 11\% of active genes. Reduction of SETD2 prevents normal loading of the FACT (FAcilitates Chromatin Transcription) complex subunits SPT16 and SSRP1, and decreases nucleosome occupancy in active genes. Moreover, co-immunoprecipitation experiments suggest that SPT16 is recruited to active chromatin templates, which contain H3K36me3-modified nucleosomes. Our results further show that within minutes after transcriptional activation, there is a SETD2-dependent reduction in gene body occupancy of histone H2B, but not of histone H3, suggesting that SETD2 coordinates FACT-mediated exchange of histone H2B during transcription-coupled nucleosome displacement. After inhibition of transcription, we observe a SETD2-dependent recruitment of FACT and increased histone H2B occupancy. These data suggest that SETD2 activity modulates FACT recruitment and nucleosome dynamics, thereby repressing cryptic transcription initiation.</p>
},
	keywords = {Cell Cycle Proteins, Cell Cycle Proteins: genetics, Cell Cycle Proteins: metabolism, DNA-Binding Proteins, DNA-Binding Proteins: metabolism, Gene Knockdown Techniques, Genetic, HEK293 Cells, HeLa Cells, High Mobility Group Proteins, High Mobility Group Proteins: metabolism, Histone-Lysine N-Methyltransferase, Histone-Lysine N-Methyltransferase: genetics, Histone-Lysine N-Methyltransferase: metabolism, Histone-Lysine N-Methyltransferase: physiology, Humans, Kinetics, Membrane Proteins, Membrane Proteins: genetics, Membrane Proteins: metabolism, Nucleosomes, Nucleosomes: metabolism, Protein Binding, RNA, RNA Polymerase II, RNA Polymerase II: metabolism, Small Interfering, Small Interfering: genetics, Transcription, Transcription Factor CHOP, Transcription Factor CHOP: genetics, Transcription Factor CHOP: metabolism, Transcription Factors, Transcription Factors: genetics, Transcription Factors: metabolism, Transcription Initiation, Transcription Initiation Site, Transcriptional Activation, Transcriptional Elongation Factors, Transcriptional Elongation Factors: metabolism, Transcriptome},
	isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
	issn = {1362-4962},
	doi = {10.1093/nar/gks1472},
	url = {https://doi.org/10.1093/nar/gks1472},
	author = {Carvalho, S{\'\i}lvia and Raposo, Ana Cl{\'a}udia and Martins, Filipa Batalha and Ana Rita Grosso and Sridhara, Sreerama Chaitanya and Rino, Jos{\'e} and Carmo-fonseca, Maria and de Almeida, S{\'e}rgio Fernandes}
}
