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2015 ; 35
(24
): 4135-46
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Genomic Determinants of THAP11/ZNF143/HCFC1 Complex Recruitment to Chromatin
#MMPMID26416877
Vinckevicius A
; Parker JB
; Chakravarti D
Mol Cell Biol
2015[Dec]; 35
(24
): 4135-46
PMID26416877
show ga
The THAP11 and ZNF143 transcription factors recognize overlapping DNA sequences
and are reported to exhibit signs of both competitive and cooperative binding.
HCFC1 serves as a scaffold protein, bridging interactions between transcription
factors, including THAP11 and ZNF143, and transcriptional coregulators. The exact
mechanism of how DNA sequences guide the recruitment of the THAP11/ZNF143/HCFC1
complex to chromatin is still controversial. In this study, we use chromosomally
integrated synthetic constructs and clustered regularly interspaced short
palindromic repeat (CRISPR)-Cas9-mediated approaches in intact cells to elucidate
the role of the DNA sequence in the recruitment of this complex and to establish
its biological relevance. We show that the ACTACA submotif, shared by both THAP11
and ZNF143, directs the recruitment of THAP11 and HCFC1 to ZNF143-occupied loci.
Importantly, its position, spacing, and orientation relative to the ZNF143 core
motif are critical for this action. CRISPR-Cas9-mediated alterations of the
ACTACA submotif at endogenous promoters recapitulated results obtained with
synthetic constructs and resulted in altered gene transcription and histone
modifications at targeted promoters. Our in vivo approaches provide strong
evidence for the molecular role of the ACTACA submotif in THAP11, ZNF143, and
HCFC1 cooperative recruitment to chromatin and its biological role in target gene
expression.
|Base Sequence
[MESH]
|Binding Sites/genetics
[MESH]
|Cell Line
[MESH]
|Chromatin/genetics
[MESH]
|Clustered Regularly Interspaced Short Palindromic Repeats
[MESH]