U.S. stock index futures point to a significantly lower open on Wall Street on Wednesday, ahead of the publication of non-farm private employment numbers amid uncertainty following the U.S. government’s partial shutdown and yet another congressional showdown over Oct. 17's debt ceiling limit.

Futures on the Dow Jones Industrial Average were down 0.66 percent, while futures on the Standard & Poor's 500 Index were down 0.69 percent and those on the Nasdaq 100 Index were down 0.66 percent.

Investors remain concerned over the continuation of the U.S. government’s shutdown -- its first in 17 years -- although there is optimism in the markets that the issue could be resolved before it negatively impacts the country's sluggish economic recovery.

“The market likes certainty. Yesterday there was uncertainty. Today there is certainty that the government is starting to shut down. Right now, we think the fundamentals of companies and the economy will not be affected by what is going on in Washington,” Mike Serio, a regional chief investment officer at Wells Fargo Private Bank, told MarketWatch.

According to analysts, the debt-ceiling issue is also affecting markets, which fear that growth could be hampered if Congress fails to increase the government borrowing limit by Oct.17.  

“However, if the government shutdown goes on for a prolonged time and the debt-ceiling issue on Oct. 17 does not get resolved, we’re going to have to go back and revisit our GDP number for the year,” Serio said.

Investors will watch the ADP National Employment Report, which is a measure of the monthly change in non-farm private employment, based on the payroll data of approximately 400,000 U.S. business clients, due to be released at 8.15 a.m. EDT. The index, which comes two days ahead of the official non-farm payroll report, is expected to increase to 180,000 for September, from 176,000 recorded in the previous month.

Investors also await New York’s NAPM index, which measures business conditions among manufacturers and non-manufacturing firms doing business in the New York area, scheduled to be released at 9.45 a.m. EDT.

In Europe, markets traded lower on Wednesday, ahead of an interest rate decision by the European Central Bank. The Stoxx Europe 600 index fell 0.61 percent, London’s FTSE 100 was down 0.84 percent, Germany's DAX-30 was down 0.52 percent and France's CAC-40 was trading down 0.69 percent

In Asia, most markets except Japan traded moderately higher tracking overnight gains on Wall Street. 

Japan’s Nikkei ended down 2.17 percent, while Australia’s S&P/ASX 200 gained 0.17 percent. Hong Kong’s Hang Seng Index gained 0.55 percent and South Korea’s KOSPI Composite index traded flat. The Shanghai Composite index in China and India’s BSE Sensex were both closed for national holidays in their respective countries.