PMID:26920047

Citation	Wani, S, Sugita, A, Ohkuma, Y and Hirose, Y' (2016) Human SCP4 is a chromatin-associated CTD phosphatase and exhibits the dynamic translocation during erythroid differentiation. J. Biochem. '
Abstract	The C-terminal domain (CTD) of the RNA polymerase II (Pol II) large subunit contains tandem repeats of the heptapeptide, Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. The CTD is subject to dynamic phosphorylation during transcription, mainly at serine residues (Ser2, Ser5 and Ser7). Regulation of CTD phosphorylation by specific kinases and phosphatases is crucial for coordinating transcription with RNA processing and histone modification. Human small CTD phosphatase 4 (SCP4), also called CTDSPL2 or HSPC129, is a putative CTD phosphatase belonging to the FCP/SCP family and implicated in control of ε- and γ-globin gene expression. Here, we report the biochemical and functional characterization of SCP4. SCP4 exhibited Ser5-preferential CTD phosphatase activity in vitro, while small interfering RNA-mediated SCP4 knockdown in HeLa cells increased phosphorylation levels of Pol II at Ser5 and Ser7, but not at Ser2. Furthermore, cell fractionation, chromatin immunoprecipitation and immunofluorescence assays revealed an exclusive localization for SCP4 in the chromatin, particularly at transcriptionally silenced chromosomal regions. Interestingly, SCP4 was gradually released from the chromatin fraction during hemin-induced erythroid differentiation of K562 cells, with concomitant cytoplasmic accumulation. Therefore, SCP4 is a unique chromatin-associated, Ser5-preferential CTD phosphatase that preferentially distributes to transcriptionally silenced gene regions and may participate in gene regulation during erythroid differentiation.
Links	PubMed Online version:10.1093/jb/mvw018
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CTSL2	Colocalizes with	GO:0005737: cytoplasm	ECO:0000314:		C		Fg. 5C Immunostaining of hemintreated cells revealed time-dependent accumulation of SCP4 in the cytoplasm.	complete CACAO 11789
HUMAN:CTSL2		GO:0008420: CTD phosphatase activity	ECO:0000314:		F		Fg 1B. SCP4 functions as a Ser5-preferential CTD phosphatase in cells.	complete CACAO 11792
HUMAN:CTSL2		GO:0004647: phosphoserine phosphatase activity	ECO:0000314:		F		Fg. 2C SCP4 can function as a Ser5-specific CTD phosphatase in cells.	complete CACAO 11795
HUMAN:CTSL2		GO:0000790: nuclear chromatin	ECO:0000314:		C		Fg. 5B dynamic SCP4 relocation from the chromatin, out of the nucleus, and towards the cytoplasm.	complete CACAO 11797

References

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