CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription

CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation chec...

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Bibliographic Details
Published in:Transcription 2015-10, Vol.6 (5), p.79-90
Main Authors: Laitem, Clélia, Zaborowska, Justyna, Tellier, Michael, Yamaguchi, Yuki, Cao, Qingfu, Egloff, Sylvain, Handa, Hiroshi, Murphy, Shona
Format: Article
Language:English
Subjects:
CCCTC-Binding Factor
CTCF
elongation checkpoint
Gene Knockdown Techniques
HeLa Cells
Humans
Life Sciences
Nuclear Proteins - metabolism
P-TEFb
Phosphorylation
Positive Transcriptional Elongation Factor B - metabolism
Proto-Oncogene Proteins c-myc - genetics
Repressor Proteins - genetics
Repressor Proteins - metabolism
Research Paper
RNA Polymerase II - metabolism
RNA Polymerase II pausing
RNA, Small Nuclear - metabolism
snRNA gene
transcription
Transcription Factors - metabolism
Transcription, Genetic
Transcriptional Elongation Factors - metabolism
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Summary:CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation checkpoint of c-myc by affecting recruitment of DRB-sensitivity-inducing factor (DSIF). CTCF knockdown also causes a termination defect on the U2 snRNA genes (U2), by affecting recruitment of negative elongation factor (NELF). In addition, CTCF is required for recruitment of positive elongation factor b (P-TEFb), which phosphorylates NELF, DSIF, and Ser2 of the RNAP II CTD to activate elongation of transcription of c-myc and recognition of the snRNA gene-specific 3' box RNA processing signal. These findings implicate CTCF in a complex network of protein:protein/protein:DNA interactions and assign a key role to CTCF in controlling RNAP II transcription through the elongation checkpoint of the protein-coding c-myc and the termination site of the non-coding U2, by regulating the recruitment and/or activity of key players in these processes.
ISSN:2154-1264
2154-1272
DOI:10.1080/21541264.2015.1095269