HGSNAT has a TATA-less promoter with multiple starts of transcription

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F16%3A00060010" target="_blank" >RIV/00023001:_____/16:00060010 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/16:10328004 RIV/00064165:_____/16:10328004

Výsledek na webu

<a href="http://ac.els-cdn.com/S0378111916305777/1-s2.0-S0378111916305777-main.pdf?_tid=b444d74e-96c6-11e6-85eb-00000aacb360&acdnat=1476969265_a390a33837c435ac9a3b73e80573c76d" target="_blank" >http://ac.els-cdn.com/S0378111916305777/1-s2.0-S0378111916305777-main.pdf?_tid=b444d74e-96c6-11e6-85eb-00000aacb360&acdnat=1476969265_a390a33837c435ac9a3b73e80573c76d</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.gene.2016.07.051" target="_blank" >10.1016/j.gene.2016.07.051</a>

Jazyk výsledku

angličtina

Název v původním jazyce

HGSNAT has a TATA-less promoter with multiple starts of transcription

Popis výsledku v původním jazyce

Acetyl-CoA:alpha-glucosaminide N-acetyltransferase (N-acetyltransferase) is a lysosomal membrane enzyme that catalyzes a key step in the lysosomal degradation of heparan sulfate. Its deficiency causes Sanfilippo syndrome type IIIC (Mucopolysaccharidosis type IIIC, MPS IIIC). Here we characterize the promoter region of HGSNAT, the gene encoding N-acetyltransferase, which is located in the pericentromeric region of chromosome 8.. Promoter fragments in antisense orientation (constructs pGL4 -20/-1305 and pGL4 +50/-1305) led to reporter activities of about 50% of the pGL4 -1305/-20 activity, implying divergent initiation of transcription at the promoter. We identified two main TSSs at positions +1 and -15 from DS-ATG using Rapid amplification of cDNA ends (5'RACE). Transcripts initiating at the TSSs thus contain only DS-ATG. Five patients from our MPS IIIC cohort (n = 23) carried the rs4523300 promoter variant and one the rs149596192 promoter variant. Both variants lowered the expression of the reporter down to 68% and 59%, respectively. However, white blood cell (WBC) N-acetyltransferase activities in individuals carrying the variants did not significantly differ from homozygotes for the wild-type alleles, suggesting only a partial impact of transcriptional regulation on N-acetyltransferase activities in vivo.

Název v anglickém jazyce

HGSNAT has a TATA-less promoter with multiple starts of transcription

Popis výsledku anglicky

Acetyl-CoA:alpha-glucosaminide N-acetyltransferase (N-acetyltransferase) is a lysosomal membrane enzyme that catalyzes a key step in the lysosomal degradation of heparan sulfate. Its deficiency causes Sanfilippo syndrome type IIIC (Mucopolysaccharidosis type IIIC, MPS IIIC). Here we characterize the promoter region of HGSNAT, the gene encoding N-acetyltransferase, which is located in the pericentromeric region of chromosome 8.. Promoter fragments in antisense orientation (constructs pGL4 -20/-1305 and pGL4 +50/-1305) led to reporter activities of about 50% of the pGL4 -1305/-20 activity, implying divergent initiation of transcription at the promoter. We identified two main TSSs at positions +1 and -15 from DS-ATG using Rapid amplification of cDNA ends (5'RACE). Transcripts initiating at the TSSs thus contain only DS-ATG. Five patients from our MPS IIIC cohort (n = 23) carried the rs4523300 promoter variant and one the rs149596192 promoter variant. Both variants lowered the expression of the reporter down to 68% and 59%, respectively. However, white blood cell (WBC) N-acetyltransferase activities in individuals carrying the variants did not significantly differ from homozygotes for the wild-type alleles, suggesting only a partial impact of transcriptional regulation on N-acetyltransferase activities in vivo.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Gene

ISSN

0378-1119

e-ISSN

—

Svazek periodika

592

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

36-42

Kód UT WoS článku

000383304600006

EID výsledku v databázi Scopus

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